To better understand the association between obesity-related biomarkers and cardiovascular dysfunction in HFpEF, researchers at Massachusetts General Hospital conducted a retrospective cohort study of participants with preserved ejection fraction and chronic dyspnea who underwent cardiopulmonary exercise tests from 2006 to 2017.

A history and physical examination, including overnight fasting phlebotomy at the time of exercise tests, were conducted for each participant. Obesity was defined as a body mass index (BMI) greater than 30 kg/m². From blood samples, the researchers measured high-sensitivity C-reactive protein (CRP), adiponectin, interleukin-6, leptin (IL-6), resistin, and insulin resistance (HOMA-IR).

Participants underwent right heart catheterization prior to exercise testing. Hemodynamic parameters were obtained at rest and during exercise. Overall exercise capacity was measured by peak oxygen consumption (VO₂). The researchers defined HFpEF on the basis of elevated left ventricular filling pressures at rest or during exercise.

The association between obesity-related biomarkers and exercise parameters was evaluated with multivariable linear regression. The researchers used Cox proportional hazard analyses to assess the association between the biomarkers and clinical outcomes. 

The study included 509 participants, of whom 228 (49%) met the clinical criteria for HFpEF. Compared with participants without HFpEF, those with HFpEF were more likely to have obesity, hypertension, and diabetes. Participants with HFpEF were also more likely to have higher baseline levels of CRP, IL-6, HOMA-IR, and leptin in addition to lower VO₂. 

The researchers found that obesity-related biomarkers were associated with overall exercise capacity (P ≤.002 for all). Higher biomarker levels were associated with worse fitness, although higher levels of adiponectin were associated with better peak VO₂. The largest effect size was seen with leptin (β, -2.35; SD, 0.19; P <.001). 

CRP, IL-6, and resistin were associated with chronotropic response (P ≤.001 for all), whereas worse HOMA-IR, lower adiponectin, and higher leptin levels were associated with greater blood pressure response (P ≤.002 for all). 

In secondary analyses, increased risk for HFpEF was significantly associated with:

• Obesity (odds ratio [OR], 1.96; 95% CI, 1.30–2.96);
• Diabetes (OR, 1.89; 95% CI, 1.04–3.41);
• Higher leptin levels (OR, 1.35; 95% CI, 1.09-1.70); and,
• Higher CRP levels (OR, 1.25; 95% CI, 1.03-1.52).

Study limitations include a lack of generalizability due to potential referral bias, the potential of confounding comorbid conditions, limited power to examine the association between the explored biomarkers and a purely obese-HFpEF phenotype, and limited associations with clinical outcomes due to sample sizes. 

The researchers concluded, “[S]pecific obesity-related pathways including inflammation, adipokine signaling, and insulin resistance may underlie the association of obesity with HFpEF and exercise intolerance.” 

Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Investigators aimed to characterize the cross-sectional and across time-relationship between patients’ health status and activity measured by a wearable smartwatch device.

The investigators used data from the CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure; ClinicalTrials.gov Identifier: NCT04252287) study. Briefly, CHIEF-HF was a randomized, controlled trial conducted from the end of March 2020 to mid-February 2021 from 18 medical centers across the US. Participants with HF completed the serial Kansas City Cardiomyopathy Questionnaires (KCCQs) and functional performance was assessed using a wearable device to test the efficacy of canagliflozin on health status.

In the current analysis, the investigators included data from 425 patients with HF (mean [SD] age, 63.5 [13.2] years; 44.5% women; 40.9% with reduced ejection fraction) and a compatible smartphone. Patients were excluded for a variety of reasons including history of diabetic ketoacidosis, type 1 diabetes, hypotension, and acute decompensated HF. Participants (83% White; 15% Black; 27.5% type 2 diabetes) completed the KCCQs through a smartphone application and were provided a Fitbit Versa 2.

Mean KCCQ-total symptom (TS) scores increased 2.5 points on average through 12 weeks and the KCCQ-physical limitation (PL) scores increased by 4.0 points through 12 weeks.

Baseline daily step count increased across the KCCQ-TS categories of scores:

• 2438 steps/d for scores of 0 to 24
• 4004 steps/d for scores of 25 to 49
• 4260 steps/d for scores of 50 to 74
• 4871 steps/d for scores 75 to 100; P <.001

Scores similarly increased across the KCCQ-PL categories of scores (2302 steps/d for scores of 0 to 24; 5351 steps/d for scores 75 to 100; P <.001). After multivariable adjustment, this relationship remained significant for KCCQ-TS and KCCQ-PL scores.

Changes in daily step count were significantly associated with nonlinear changes in KCCQ-TS scores (P =.004) and with nonlinear changes in KCCQ-PL scores (P =.003). This nonlinear association was primarily seen with daily step counts of less than 5000 steps. Little association was found between KCCQ scores and step counts greater than 5000 steps/d.

The investigators stated that daily floors climbed was not significantly different across 25-point ranges of KCCQ-TS scores or KCCQ-PL scores, and floors climbed was associated with baseline KCCQ scores alone.

Significant study limitations include commercially available wearable devices may not be optimal for measuring functional performance in patients with HF. There is also lack of data on comorbidities and the inability to quantify external factors (ie inclement weather’s affect on step count).

“Daily step count was nonlinearly associated with health status at baseline and over time in patients with heart failure,” the investigators wrote.

Disclosure: This research (CHIEF-HF) was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The post hoc analysis of the EMPHASIS-HF (ClinicalTrials.gov Identifier: NCT00232180) trial assessed the efficacy and safety of eplerenone in patients based on HFrEF duration.

Participants were aged 55 years or older with New York Heart Association functional class II symptoms, left ventricular ejection fraction of 30% or less, and were being treated with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or both and a β-blocker (unless contraindicated) at the recommended dose or maximally tolerated dose.

Participants were randomly assigned to receive eplerenone (up to 50 mg daily) or placebo in addition to recommended therapy. HF duration was classified into 3 groups: less than 1 year, 1 to less than 5 years, and 5 years or longer. The primary outcome was the time to first occurrence of the composite of cardiovascular death or HF hospitalization.

The cohort included 2732 patients with HFrEF, mild symptoms, and data on HF duration. The median HF duration was 2.4 years (IQR, 0.4-7.0 years). The number of patients in each HF duration category was 975 (35.7%; mean age, 67.8±7.6 years) in the less than 1 year group, 769 (28.1%; mean age, 68.2±7.7 years) in the 1 to less than 5 years group, and 988 (36.2%; mean age, 69.8±7.5 years) in the 5 years or longer group. The median follow-up was 21 months. Patients who had a longer HF duration were more frequently men and older.

The incident rate per 100 patient-years of the composite of cardiovascular death or hospitalization for HF increased with greater HF duration. In the less than 1 year group it was 9.8 (95% CI, 8.4-11.4). In the 1 to less than 5 years group it was 13.5 (95% CI, 11.6-15.7). In the 5 years or longer group it was 17.6 (95% CI, 15.6- 19.8).

The benefit of eplerenone was consistent for all outcomes according to HF duration. The overall adjusted hazard ratio (HR) for eplerenone vs placebo for the primary outcome was 0.64 (95% CI, 0.54-0.76). For the less than 1 year group, the HR was 0.59 (95% CI, 0.42-0.82), for the 1 to less than 5 years group the HR was 0.72 (95% CI, 0.52-1.00), and in the 5 years or longer group, the HR was 0.59 (95% CI, 0.46-0.76; P_interaction =.54).

The number needed to treat (NNT) for the median trial duration regarding the primary outcome was 10 (95% CI, 8-14) for HF duration of 5 years or longer vs 14 (95% CI, 11-21) for HF duration of less than 1 year and 13 (95% CI, 10-19) for HF duration of 1 to less than 5 years. The NNT for all-cause mortality was 24 (95% CI, 15-95) for HF duration of 5 years or longer vs 34 (95% CI, 21-136) for HF duration of less than 1 year and 31 (95% CI, 19-125) for HF duration of 1 to less than 5 years.

The researchers noted that their study is not a prespecified analysis, and HF duration was obtained from questions on a case report form and was not independently verified. Also, the results may not be generalizable to all patients with HFrEF, and separate Cox regression analyses were conducted for each subpopulation based on HF duration, which may have affected the estimation of HRs.

“Eplerenone was efficacious and safe in patients with long-standing HFrEF, who obtained substantial reductions in mortality and morbidity with this treatment,” wrote the investigators. “MRA [mineralocorticoid receptor antagonist] treatment should be considered in all patients with HFrEF, regardless of the duration of HF.”

Disclosure: The EMPHASIS-HF trial was sponsored by Pfizer. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The Biden administration announced Tuesday that the drugmakers, including Merck, Bristol Myers Squibb, and Johnson & Johnson, will take part in price negotiations despite ongoing lawsuits over this same requirement, NBC News reported.

This negotiation is a component of the Inflation Reduction Act, which allows Medicare to work with the drug companies to reduce prices for older Americans. Negotiations are to occur next year with resulting prices going into effect in 2026.

The first 10 drugs named by the Centers for Medicare & Medicaid Services include diabetes drug Januvia, Enbrel for rheumatoid arthritis, and the blood thinners Eliquis and Xarelto. Last year, about 9 million Medicare enrollees paid $3.4 billion out of pocket for these 10 specific drugs, NBC News reported. Additional drugs will later be added to negotiations.

The federal government had given manufacturers one month to decide if they would participate in talks or face tax penalties, NBC News reported. Drugmakers could avoid the penalty if they remove their drug from the Medicare program, but that, too, could be costly.

Companies that are suing, including Merck and Johnson & Johnson, have said that allowing negotiations could affect their profits and, as a result, spending on research and development.

NBC News Article

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Researchers conducted a meta-analysis using individual participant data from 3 long-term, placebo-controlled, double-blind, randomized clinical trials (CONFIRM-HF, AFFIRM-AHF, and HEART-FID). The trials included adult patients with HF and iron deficiency, used FCM as an active treatment for iron deficiency, had 52 weeks or longer of follow-up, and prospectively reported outcomes including first and recurrent HF and CV hospitalizations, CV death, and all-cause death. A systematic review was performed in PubMed for trials published between July 19, 2013, and July 18, 2023, and the results of the IRONMAN trial were included in a sensitivity analysis.

The prespecified coprimary efficacy endpoints were a composite of recurrent CV hospitalizations and death for any CV reason and a composite of recurrent HF hospitalizations and CV death at 52 weeks.

The 3 trials randomly assigned 4501 patients to receive FCM (n=2251) or placebo (n=2250). The cohort had a mean age of 69.2 (SD 11.0) years, a mean LVEF of 31.6% (SD 8.1%), and 63% were men.

FCM therapy significantly decreased the coprimary composite endpoint of CV death and total CV hospitalizations vs placebo (rate ratio [RR], 0.86; 95% CI, 0.75-0.98; P =.029), without evidence of trial heterogeneity. A similar trend toward a decrease of the coprimary composite endpoint of CV death and total HF hospitalizations also was observed (RR, 0.87; 95% CI, 0.75-1.01; P =.076), without evidence of trial heterogeneity.

FCM therapy was associated with a 17% relative rate reduction in total CV hospitalizations (RR, 0.83; 95% CI, 0.73-0.96; P =.009) as well as a 16% relative rate reduction in total HF hospitalizations (RR, 0.84; 95% CI, 0.71-0.98; P =.025). FCM therapy did not affect the time to CV death (hazard ratio [HR], 0.97; 95% CI, 0.80-1.17; P =.72).

In subanalyses, evidence was observed for a significant interaction between transferrin saturation (TSAT) and the composite of CV hospitalization and CV death (P_interaction =.019) and for CV death (P_interaction =.035). Participants in the lowest TSAT tertile (<15%) had a greater treatment effect compared with those who had a higher baseline TSAT. A similar pattern occurred regarding the effect of TSAT on total HF hospitalizations and CV death (P_interaction =.095).

FCM therapy was associated with a decreased time to first CV death or HF hospitalization by 12% (HR, 0.88; 95% CI, 0.78-0.99; P =.039) as well as the time to first CV death or CV hospitalization by 11% (HR, 0.89; 95% CI, 0.80-0.99; P =.033).

The FCM and placebo groups had rates of serious treatment-emergent infections of 9.9 per 100 patient-years and 9.6 per 100 patient-years, respectively. No deaths were reported as resulting from serious treatment-related treatment-emergent adverse events.

Among several limitations, the researchers did not have access to the individual participant data from the IRONMAN trial, and the follow-up was limited to 12 months in the main analyses. “Importantly, our findings support continued research to identify those patients who are most likely to benefit from treatment with intravenous iron, particularly as it relates to the criteria used to identity ID [iron deficiency] and eligibility for initial and repeat iron doses,” the investigators wrote.

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The meta-analysis evaluated the effect of MRA use on the CV effects of SGLT2 inhibitors in patients with HF regardless of ejection fraction (EF).

Investigators search the PubMed/MEDLINE, Embase, and Web of Science databases and clinical trial registries for relevant randomized controlled trials (RCTs) or post-hoc analyses of RCTs through February 4, 2023. Eligible studies included adults (aged ≥18 years) with HF regardless of EF and diabetes status with a duration of 6 months or longer and an intervention group treated with 1 SGLT2 inhibitor as monotherapy or add-on to baseline medications and a comparator group treated with placebo. The main outcomes were the composite of HHF/CV death, HHF, and CV death.

The analysis included 5 studies with 21,947 patients who had HF. Sotagliflozin was used in 1 study and the other 4 studies were post-hoc analyses of RCTs on empagliflozin and dapagliflozin.

In the pooled analysis, randomization to SGLT2 inhibitor treatment vs placebo was associated with a decreased risk for HHF/CV death among patients with HF treated with MRAs (hazard ratio [HR], 0.75; 95% CI, 0.68-0.81) or without MRAs (HR, 0.79; 95% CI, 0.72-0.86; P =.43 for subgroup differences).

SGLT2 inhibitors had a similar decrease compared with placebo for the risk for HHF in patients with chronic HF who were or were not using MRAs at baseline (HR, 0.74; 95% CI, 0.67-0.83; vs HR, 0.71; 95% CI, 0.63-0.80; P_interaction =.53).

SGLT2 inhibitors reduced CV death compared with placebo among only patients with chronic HF treated with MRAs (HR, 0.81; 95% CI, 0.72-0.91) but not for MRA nonusers (HR, 0.98; 95% CI, 0.86-1.13). A greater relative reduction was indicated in CV death in patients with chronic HF regardless of EF who were randomly assigned to SGLT2 inhibitors and receiving MRA (P =.034 for subgroup differences).

SGLT2 inhibitors compared with placebo reduced all-cause mortality in the HF subgroup with MRA use (HR, 0.90; 95% CI, 0.81-0.99), but not in those without MRA use at baseline (HR, 0.97; 95% CI, 0.88-1.08). No subgroup differences were observed in SGLT2 inhibitor effects based on MRA use (P_interaction =.27).

For participants who received SGLT2 inhibitors, renal adverse events were comparable in MRA users vs nonusers (relative risk [RR], 0.83; 95% CI, 0.68-1.01). A similar observation occurred among patients randomly assigned to placebo (RR, 0.97; 95% CI, 0.80-1.17). SGLT2 inhibitors appeared to reduce the risk for mild hyperkalemia (P_interaction <.001) and severe hyperkalemia (P_interaction =.051) associated with use of MRA.

Among several limitations, participants were randomized for SGLT2 inhibitors use but not for MRA use. In addition, the data for previous MRA use are unavailable for patients who were not on MRAs at baseline, the analysis did not account for changes in MRA use during the follow-up, and the duration of differential use of MRAs was unknown.

“Combination of SGLT2i [inhibitors] and MRA may offer a potential disease-modifying strategy with lower risk of treatment-emergent hyperkalemia in people with chronic HF regardless of EF,” wrote the study authors. “These hypothesis-generating findings require prospective testing with adequately powered randomized controlled trials.”

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Researchers sought to determine whether the efficacy and safety of dapagliflozin in HF were consistent across geographic regions using data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) randomized placebo-controlled trials.

Both trials enrolled patients diagnosed with HF who had New York Heart Association functional class II to IV and increased natriuretic peptide levels. Patients with a left ventricular ejection fraction (LVEF) of 40% or less were randomized in DAPA-HF, and those with an LVEF of more than 40% were randomized in DELIVER.

Patients were enrolled in 20 countries in each trial and were classified into 4 geographic regions: Europe, North America, South America, and Asia. The primary outcome in the 2 trials was the composite of worsening HF or death of cardiovascular causes.

The pooled data set included 11,007 patients, of whom 5503 were assigned to placebo and 5504 to dapagliflozin. Of the cohort, 46.9% were enrolled in Europe, 13.9% in North America, 18.2% in South America, and 21.1% in Asia. Asian patients were younger (mean age, 67.6 years) than those in South America (mean age, 68.3 years), Europe (mean age, 70.0 years), and North America (mean age, 71.2 years).

Patient outcomes varied by geographic region, but the efficacy of dapagliflozin did not vary. The primary outcome rate according to geographic regions was greater in North America (13.9; 95% CI, 12.5-15.4) compared with Europe 10.8 (95% CI, 10.1-11.5), Asia 10.5 (95% CI, 9.5-11.5), and South America 10.0 (95% CI, 9.0-11.1).

North America had the highest rate of worsening HF events and rates of total HF hospitalizations. South America had the highest rate of unadjusted and adjusted cardiovascular and all-cause mortality, and Asia had the lowest rates.

The hazard ratio for dapagliflozin vs placebo for the primary endpoint was 0.85 (95% CI, 0.75-0.96) in Europe, 0.75 (95% CI, 0.61-0.93) in North America, 0.72 (95% CI, 0.58-0.89) in South America, and 0.74 (95% CI, 0.61-0.91) in Asia (P _interaction =.40). For LVEF of 40% or less the P_interaction was .39, and for LVEF of greater than 40% the P_interaction was .84. The effect of dapagliflozin was consistent regardless of LVEF in each region.

North American patients were most likely, and South American patients least likely, to discontinue randomized treatment for any reason (placebo group, 21.8% in North America vs 6.4% in South America). Patients receiving placebo and dapagliflozin had similar safety profiles in each region.

Among several study limitations, the participants were selected according to specific trial inclusion and exclusion criteria, and the results may not be generalizable to all patients with HF. In addition, patients were unavailable from Africa, and the analysis cannot account for many potential influences on outcomes, including climate and other environmental factors, diet, and lifestyle.

“Further efforts are needed to assure equitable access to sodium-glucose cotransporter-2 inhibitor therapy for patients with HF around the world,” wrote the investigators.

Disclosure: The DAPA-HF and DELIVER trials were funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Investigators sought to assess the effect of baseline frailty burden on the efficacy of ICD therapy for preventing death among patients with HFrEF. All-cause mortality was the primary outcome. Cardiovascular (CV) death, sudden cardiac death (SCD), and all-cause hospitalization were secondary outcomes.

They conducted a post hoc analysis using participant-level data from 1676 participants with HFrEF (mean age, 59±12 years; 23% women) from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). SCD-HeFT was a multicenter, randomized controlled trial that included participants with HF and left ventricular ejection fraction of no greater than 35% and New York Heart Association functional class II or III. Participants were randomly assigned in a 1:1:1 ratio to ICD therapy, amiodarone, or placebo. ICD therapy consisted of a shock-only single-lead device programmed to detect tachycardia (defined as 18 or 24 beats at a rate of 187 beats/min or higher). In the post hoc analysis, participants from the amiodarone treatment arm were excluded.

The investigators of the post hoc analysis used the Rockwood Frailty Index (FI) to estimate baseline frailty, then participants were stratified into high vs low frailty burden groups (FI > median vs FI ≤ median, respectively). At baseline, participants in the high frailty group vs low frailty group tended to be younger, with a higher burden of HF symptoms, traditional CV risk factors, and worse functional status.

Median FI for the high frailty group was 0.54 (IQR, 0.47-0.60) and median FI for the low frailty group was 0.30 (IQR, 0.23-0.37). In adjusted multivariable Cox models, the investigators found the treatment effect of ICD therapy for risk of all-cause mortality was significantly modified by baseline frailty status (P_interaction =.047). The treatment effect was significant for CV mortality (P_interaction =.02) but not statistically significant for sudden cardiac death (P_interaction =.11) or all-cause readmission (P_interaction =.54).

Median follow-up was 3.4 years (IQR, 2.5-4.0 years) and 25.4% of participants died during follow-up. Participants with high frailty vs low frailty had a significantly higher cumulative incidence of all-cause mortality. High vs low frailty burden was associated with a 45% higher risk of all-cause mortality (HR, 1.45; 95% CI, 1.20-1.76; P <.001) in unadjusted analysis.

Among participants with low frailty burden, ICD therapy was associated with a lower risk of all-cause mortality (hazard ratio [HR], 0.56; 95% CI, 0.40-0.78) compared with participants with high frailty burden (HR, 0.86; 95% CI, 0.68-1.09).

Limitations of the analysis include lack of generalizability beyond patients who meet SCD-HeFT enrollment criteria and SCD-HeFT was conducted more than 20 years ago, therefore the analysis cannot account for evolving medical therapy.

“Among participants with HFrEF enrolled in SCD-HeFT, frailty modified the effect of ICD therapy on all-cause mortality such that adults with a lower vs higher burden of frailty appeared to derive greater benefit,” the study authors wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Pascal M. Burger, from the University Medical Centre Utrecht in the Netherlands, and colleagues developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for predicting lifetime risk and treatment benefit in patients with HFrEF. The model was developed in 15,415 participants from the PARADIGM-HF and ATMOSPHERE trials. External validation was performed in 51,286 participants in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial.

The researchers found adequate calibration of two- to 10-year risk, and the c-statistics were 0.65 to 0.74, respectively. The model was combined with hazard ratios from trials to allow estimation of an individual’s (lifetime) risk and treatment benefit. Combined treatment with a mineralocorticoid receptor antagonist, sodium-glucose cotransporter 2 inhibitor, and angiotensin receptor-neprilysin inhibitor was estimated to afford a median of 2.5 and 3.7 additional years of overall and heart failure hospitalization-free survival, respectively, by applying the tool to the development cohort.

“The model could serve as a tool to improve the management of patients with HFrEF by facilitating personalized medicine and shared decision-making,” the authors write. Several authors disclosed ties to the pharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)

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The multicenter, retrospective, cohort study enrolled patients aged 18 years or older with ccTGA, who were seen at least twice at an adult congenital heart disease (ACHD) outpatient clinic during a period of a year or longer.

An initial visit was defined as the first outpatient ACHD encounter since January 1, 2002, and the primary outcome was the first occurrence of mechanical circulatory support (MCS), heart transplantation, or death.

The analysis included 558 patients (48% women) from 29 centers. The participants had a median age of 32.8 (IQR, 23.5-47.1) years at their initial visit and 42.1 (IQR, 32.5-55.6) years at their last follow-up.

The mean follow-up was 8.7±4.9 years (1.0-19.1 years) and was comparable between those who did and those who did not have a primary outcome event. A total of 75 individuals had a primary outcome event (13.4%; 95% CI, 11%-17%; 15.4 events per 1000 person-years), including 11 MCS implantations, 12 transplantations without MCS, and 52 deaths without previous MCS or transplantation.

The proportion of patients who had a primary outcome event increased with age, from 4.2 (95% CI, 1.6%-6.7%) for those aged younger than 30 years to 34.6 (95% CI, 16.3-52.9) for those aged 60 to 70 years.

Participants who had a primary outcome event were older at their initial visit, were more likely to have diabetes, and had greater weight and body mass index (BMI). The primary outcome also was more common in those who were taking beta-blockers and those who had a higher prevalence of atrial arrhythmia before their initial visit.

After exclusion of patients with tricuspid valve replacement before their initial visit (n=62), event rates were lowest in patients with right ventricular (RV) dysfunction and tricuspid regurgitation (TR) in the normal-mild range (13/181, 7%) and highest in those with RV dysfunction and TR in the moderate-severe range (31/110, 28%, P <.001, not accounting for follow-up duration).

Participants who had a primary outcome were more likely to have initiated a loop diuretic (32% vs 13%, P <.001) or an aldosterone antagonist (28% vs 11%, P <.001) during the follow-up period.

Multivariable modeling with initial visit findings showed that the only independent predictors of the composite primary outcome were older age at initial visit (hazard ratio [HR], 1.44 per decade; 95% CI, 1.21-1.70; P <.001), previous heart failure admission (HR, 4.44; 95% CI, 2.61-7.56; P <.001), and severe RV dysfunction designation by echocardiography (HR, 3.50; 95% CI, 1.98-6.21; P <.001). Atrial arrhythmia, ventricular arrhythmia, QRS duration, beta-blocker use, diuretic use, and estimated glomerular filtration rate were not independently predictive.

Among several limitations, survivorship and referral bias affected the sample, and the population is skewed toward younger participants. Also, practice patterns vary between centers, and variation likely occurred regarding frequency of testing and use of medications. Furthermore, the multivariable modeling for risk calculation is limited in part because of missing data such as QRS duration, exercise, or cardiovascular magnetic resonance findings.

“Despite the relatively large multicenter cohort, it remains difficult to reliably predict which patients are most likely to rapidly progress towards end-stage heart failure,” wrote the study authors. “Additional analyses of this dataset will further elucidate predictors for worse outcomes in ccTGA patients.”

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The pooled cohort analysis obtained participant-level data from the Atherosclerosis Risk in Communities and the Multi-Ethnic Study of Atherosclerosis cohorts. The participants did not have history of cardiovascular disease and had cystatin C and creatinine data available.

The primary outcome was adjudicated incident heart failure during a 10-year follow-up. Multivariable adjusted Cox regression models were used to determine the 10-year risk for incident heart failure with eGFR overall and stratified by race.

A total of 15,615 individuals without prevalent cardiovascular risk were included in the study, of whom 45.0% were men and 23.9% were Black. The median age was 62 years. The participants had a median eGFR_cr-cys and eGFR_cr of 91.4 mL/min/1.73 m² and 84.7 mL/min/1.73 m², respectively. The first, second, third, and fourth quartiles of the eGFR_cr-cys were less than 79.4 mL/min/1.73 m², 79.4 to 91.4 mL/min/1.73 m², 91.4 to 102.0 mL/min/1.73 m², and greater than 102.0 mL/min/1.73 m², respectively.

Overall, 879 incident heart failure events occurred, for an incidence rate of 6.1 (95% CI, 5.8-6.6) events per 1000 person-years. The estimated risk for incident heart failure was increased with use of the eGFR_cr-cys vs the eGFR_cr of less than 90 mL/min/1.73 m².

The multivariable-adjusted risk for incident heart failure was 1.02 (95% CI, 0.80-1.30) in the third quartile, 1.02 (95% CI, 0.80-1.30) in the second quartile, and 1.47 (95% CI, 1.16-1.86) in the first quartile, using the highest quartile of eGFR_cr-cys as the reference group.

The adjusted hazard ratio for incident heart failure was 0.90 (95% CI, 0.73-1.12) in the third quartile, 0.96 (95% CI, 0.77-1.20) in the second quartile, and 1.15 (95% CI, 0.93-1.44) in the first quartile, with the highest quartile of eGFR_cr used as the reference group.

The C-index was 0.8029 (0.7886-0.8172) with the eGFR_cr and 0.8046 (0.7903-0.8189) with the eGFR_cr-cys in the Cox models for incident heart failure. For patients who were not Black, the C-index for Cox models predicting the risk for incident heart failure was 0.8077 (0.7908-0.8246) for the eGFR_cr and 0.8090 (0.7921-0.8259) for the eGFR_cr-cys.

In Black patients, the C-index for Cox models predicting the risk for incident heart failure was 0.7944 (0.7674-0.8214) with the eGFR_cr and 0.7976 (0.7709- 0.8243) with the eGFR_cr-cys.

The researchers noted that the study combined cohorts that were demographically and clinically different, and the validation cohorts had a limited number of Black individuals and insufficient representation of individuals who were not White or Black. In addition, the study did not stratify heart failure based on ejection fraction owing to limited data, and unmeasured residual confounding is possible.

“Widespread use of race-independent creatinine and cystatin C-based eGFR may help mitigate health disparities by improving access to heart failure therapy in previously ineligible individuals,” wrote the study authors.

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The analysis aimed to characterize the associations of sex and age with background standard HF therapies (guideline-directed medical therapy and HF devices), clinical features, outcomes, and response to treatment with vericiguat among participants in the VICTORIA trial (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction [HFrEF]).

VICTORIA (ClinicalTrials.gov Identifier: NCT02861534) was an international, multicenter, placebo-controlled trial exploring the efficacy and safety of vericiguat in symptomatic chronic HF with ejection fractions (EFs) less than 45% and worsening HF events within 6 months. Patients (N=5050) were randomly assigned 1:1 to start 2.5 mg vericiguat or matching placebo, then up-titrated to 5 mg then to 10 mg once daily. Composite of time to first HF hospitalization or cardiovascular death was the primary endpoint.

In the post hoc analysis, study authors compared clinical characteristics across sex (24% women) and age groups (younger than 65 [n=1873], 65 to younger than 75 [n=1609], 75 and older [n=1568] years of age). The proportion of women in age groups increased from 20% to 24% to 28%, respectively. Compared with men, women in each group had shorter intervals from HF diagnosis to randomization, higher EFs, and lower burden of coronary artery disease, hyperlipidemia, and atrial fibrillation, but similar N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels.

Study authors found that overall, when compared with younger patients, individuals 75 years of age had worse kidney function, higher NT-proBNP levels, and more class III and class IV symptoms, but had the lowest use of triple therapy (guideline-directed medical therapy). Older patients were less likely to achieve target doses of triple therapy, but by age, there were no sex differences in triple therapy.

Study authors noted men at least 75 years of age were more than twice as likely to receive defibrillators and 65% more likely than women to undergo cardiac resynchronization. Women compared with men across all age groups had nominally lower primary composite outcomes.

There were no between-sex differences in any age group in vericiguat dosing, and age did not modify the beneficial effect on the primary outcome (continuous age, P_interaction =0.169; categorical age, P_interaction =0.189), nor did sex (P_{3-way interaction} =0.847).

Current post hoc analysis limitations include the post hoc design and selection bias.

“Although elderly women received less intense background HF therapy than men, their prognosis was nominally better,” study authors concluded, adding, “The benefit of vericiguat was independent of age and sex.”

Disclosure: This research was supported by Merck Sharp and Dohme Corp and Bayer AG. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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According to guidelines, patients hospitalized with heart failure should have an ambulatory follow-up visit within 1 to 2 weeks of discharge. This recommendation is not only best practice, but it is critical. Dire statistics plague heart failure patients, including an average 25% readmission rate within 30 days of discharge and a 33% fatality rate in the year following hospitalization.¹

A study published in 2023 revealed that timely follow-up simply isn’t happening for most patients in underserved populations. When analyzing the Medicaid data of 9859 patients with diabetes and heart failure in Alabama, researchers found that about 31% of patients completed their postdischarge visit late (within 60 days), and almost 27% had no visit. In addition, the vast majority (over 70%) followed up with their primary care doctor, while only 12% saw a cardiologist.²

Social barriers, such as lack of transportation and limited access to medical care, increase heart failure complications and readmission rates.³ By understanding the impact of these social determinants of health, progress can be seen for reducing heart failure, a disease impacting over 6.5 million Americans, leading to over 1.9 million hospitalizations, and costing the country at least $31 billion each year.⁴ Here’s why so many patients never make it to their postdischarge appointment and how successful programs are testing blueprints to reverse the trend.

What Are the Social Determinants of Health?

The social determinants of health are the conditions that impact health care outcomes beyond an individual’s clinical risk factors. These encompass 5 domains: economic stability, education access and quality, health care access and quality, neighborhood and built environment, and social and community context.

Read more: Patient Education

Social determinants of health may also be viewed as the “conditions in which people are born, live, learn, work, play, worship, and age.”³

There are many well-established connections between the social influences of health. Data published in 2021 by the World Health Organization estimated that 30% to 55% of health outcomes are directly related to social determinants of health.³ The American Heart Association has also acknowledged the impact of social factors, like environment, lifestyle, and stress, on chronic disease management, calling for individual and neighborhood-wide initiatives. Patients require more support with both navigating the health care system and learning to care for their chronic conditions at home.

As researchers narrow the focus to heart failure, more opportunities for progress arise. For example, poverty increases toxic stress associated with physical consequences like high blood pressure and inflammation.³ Unsafe neighborhoods limit outdoor exercise, and substandard education reduces health literacy and the ability to manage chronic conditions. Additionally, patients with a network of support are more likely to have caregivers, help with transportation, and lower levels of anxiety and depression.³ While there are no easy fixes for these complex issues, better data enables the design of value-based care models for holistic patient care.

Challenges in Quantifying the Problem

Despite the value of social data, it is not always easy to measure. For instance, some studies rely on whether the patient is married or has children to determine their level of social support. While this information can be readily sourced from electronic medical records (EMR), it is not necessarily validated or guaranteed to paint an accurate picture. Current EMRs are not necessarily designed to capture the many social determinants of health that exist. Therefore, collecting less concrete information, like a patient’s level of spirituality, remains a challenge.³

In addition, patients are multifaceted and don’t always fit neatly into a box based on their social determinants of health. Characteristics overlap and interact, such as race, sex, and income. While associations with outcomes like heart failure follow-up are helpful, they tend to fall short of producing a comprehensive patient profile. Fortunately, there’s no harm in providing interventions that help patients schedule appointments, get easier access to care, and learn how to manage their health. Taking a more proactive and hands-on approach offers potential payoffs for heart failure patients from all walks of life.

Effective Interventions Worth Repeating

A study on 261 heart failure patients reviewed how interventions can produce significantly higher rates of postdischarge follow-up. Those in the intervention group had a 40% referral rate and 24% completion of a cardiology visit within 7 days of discharge, compared to just 12% referral rate and 10% completed visit in those receiving standard care. By 14 days postdischarge, 55% of the intervention group had a scheduled appointment versus 31% of nonintervention patients. Not only was the intervention successful in boosting timely postdischarge visits, but it was also associated with a 41% lower rate of emergency department visits, all-cause hospitalizations, and deaths 30 days after discharge.¹

To achieve these promising results, researchers implemented a transitional care pathway at the Phoenix Veteran’s Affairs Medical Center.¹ They asked the hospitalist team to refer all patients admitted with a primary diagnosis of heart failure within 7 to 14 days postdischarge. In the triage process, a heart failure clinic consult was created for these patients, prompting a meeting with the cardiology nurse before discharge. During this visit, the nurse instructed the patient on self-care, providing them with a blood pressure cuff and a scale. The nurse also ordered laboratory tests and scheduled a postdischarge heart failure clinic appointment. Patients were given the clinic’s contact information and daytime access to the nurse by phone to answer questions, refill medications, facilitate clinic scheduling, and address any concerns once they returned home. The clinic had 12 spots each week where patients could meet with a newly hired cardiologist or 1 of 3 preexisting nurse practitioners. In addition, telehealth monitoring and Veterans Health Administration home nursing services were available.

This study is just one example of how a targeted intervention can improve outcomes for heart failure patients. Intentionally reaching patients, even using existing resources, can make all the difference in overcoming barriers and raising short-term monitoring and survival rates. Providing a nurse liaison, patient resources, and increasing clinic capacity greatly impacted how many patients ended up with timely follow-ups. Continued research on the long-term effects of this type of intervention can help quantify the value of heart failure interventions, both in health care dollars and quality of life measures.

Can Specialists Be All Things to All People?

Ultimately, medical care cannot be effective without reaching the patients that need it. No matter the specialist’s skill set or the advancements in medical technology, sometimes there is no substitute for supportive nursing staff and a clinic with the capacity to see more patients. Heart failure statistics show that there is still much work needed to keep patients from falling through pivotal gaps in care. Robust health care networks must utilize social workers, nursing staff, and community resources to ensure the welfare of their patients after they leave the hospital.

Specifically, vulnerable heart failure patients must be reached in the early days postdischarge to reduce readmissions and improve survival rates.¹ From redesigning EMRs to include the social determinants of health to implementing comprehensive outreach programs initiated before discharge, efforts along the health care continuum can save future burdens to the medical system and the individual patients it serves. If “an ounce of prevention is worth a pound of cure,” initiatives for better follow-up care in postdischarge heart failure patients is well worth the initial investment.

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According to the Company, bottles labeled with the 0.125 mg dosage strength contain the 0.25 mg strength tablets and those labeled with the 0.25 mg dosage strength actually contain 0.125mg strength tablets. Patients can differentiate the strengths by the tablet appearance. The 0.125 mg strength tablet is yellow, circular, beveled, uncoated, and scored. It is marked with “N” and “201” on one side and is plain on the other side. The 0.25 mg strength tablet is white to off-white, circular, beveled, uncoated, and scored. It is marked with “N” and “202” on one side and is plain on the other side.

Digoxin is indicated for the treatment of mild to moderate heart failure in adults and to increase myocardial contractility in pediatric patients with heart failure. It is also approved for the control of ventricular response rate in adult patients with chronic atrial fibrillation. A label mix-up may result in a patient receiving either a super potent or sub potent dose, which may lead to significant adverse events. At this time the Company has not received any reports of injury related to this recall. 

The recalled products include the following lots:

• Digoxin 0.12 5mg Tablet – NDC 10135-0747-01, lot# E3810, expiration 2/2025;

• Digoxin 0.25 mg Tablet – NDC 10135-0748-01, lot# E3811, expiration 2/2025.

These products were distributed nationwide. Consumers with questions should contact Marlex Pharmaceuticals at 302-328-3355 or at 888-582-1953.

Adverse reactions related to this recall should be reported to the FDA’s MedWatch program.

The post Label Mix-Up Prompts Recall of Heart Failure Medication appeared first on The Cardiology Advisor.

Investigators sought to assess the yearly rate of mortality and related factors in patients with TGA and a systemic right ventricle. Secondary outcomes included incidence of HF hospitalization and arrhythmia.

They conducted a systematic review and meta-analysis using the Web of Science, Scopus, EMBASE, and PubMed databases without language restriction from inception to June 2022 to search for studies reporting the association of systemic right ventricle with mortality and a minimum of 2 years of follow-up during adulthood.

The investigators included 56 studies with, overall, 5358 patients at least 16 years of age with a systemic right ventricle (Dextro-TGA [D-TGA]) who have undergone either the Mustard or Senning atrial switch procedure, or congenitally corrected (cc) TGA with average follow-up of 7.27 years (at least 2 years follow-up during adulthood). Patients who had received an atrial switch operation resulting in the left ventricle at the systemic position were excluded.

Per 100 patients per year, incidence of mortality was 1.3 (95% CI, 1.0-1.7) and this incidence was not associated with mean age at baseline (odds ratio [OR], 1.03; 95% CI, 0.99-1.07). After adjusting for age, no difference was found between incidence of mortality in patients with TGA after atrial switch per 100 patients per year (OR, 1.1; 95% CI, 0.7-1.7) and patients with ccTGA per 100 patients per year (OR, 1.9; 95% CI, 1.3-2.9).

The incidence of HF hospitalization was 2.6 per 100 patients per year (95% CI, 1.9-3.7) and this incidence was not associated with mean age at baseline (OR, 1.06; 95% CI, 0.98-1.14). After adjusting for age, patients with ccTGA had higher incidence of HF hospitalization (OR, 4.3; 95% CI, 2.7-6.6) vs patients with TGA and atrial switch (OR, 3.2; 95% CI, 2.3-4.4).

Among patients with TGA and atrial switch and patients with ccTGA, no difference was found in incidence of ventricular arrhythmia per 100 patients per year.

Investigators noted predictors of poor outcome included higher plasma concentrations of N-terminal pro-brain natriuretic peptide (standardized mean difference [SMD], 1.24; 95% CI, 0.49-1.99), New York Heart Association functional class of at least 2 (risk ratio, 2.31; 95% CI, 1.57-3.39), as well as lower left ventricular ejection fraction (LVEF; SMD, -0.43; 95% CI, -0.77 to -0.09) and right ventricular ejection fraction (RVEF; SMD, -0.85; 95% CI, -1.35 to -0.35).

Limitations of the study include the heterogeneity of reported variables.

“TGA patients with a systemic right ventricle have increased incidence of mortality and HF hospitalization,” the investigators wrote.

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Investigators sought to compare implant-based multiparameter remote monitoring vs standard of care for guided HF management. A composite of HF hospitalizations and all-cause death was the primary outcome. HF hospitalizations and all-cause death considered independently were the secondary endpoints.

The investigators conducted a systematic review and meta-analysis searching Embase, CENTRAL, and PubMed databases for articles comparing implant-based multiparameter-guided management for HF vs standard of care in randomized controlled trials (RCTs) without restriction for publication date, language, or follow-up duration. They included 6 RCTs (TRUST, REM-HF, IN-TIME, RESULT, TELECART, ECOST) in a meta-analysis (N=4869) with an average of 18 months of follow-up (n=2674 multiparameter-guided management; n=2195 standard of care). The Cochrane Collaboration risk-of-bias tool was used to assess risk of bias and determined 3 studies had low risk and 3 studies had some risk.

Implant-based remote monitoring vs standard of care significantly reduced the independent events of HF hospitalization (incidence rate ratio [IRR], 0.75; 95% CI, 0.61-0.93; P =.007) and all-cause death (IRR, 0.80; 95% CI, 0.66-0.96; P =.017) resulting in significantly reduced risk of the primary composite outcome (IRR, 0.83; 95% CI, 0.71-0.99; P =.033, I²=40%). HF hospitalizations were not reported by 2 of the studies (TRUST, REM-HF).

No trial exerted excessive influence on the pooled estimate for HF hospitalizations in leave-1-out sensitivity analyses. However, non-significance was reached for all-cause death when the IN-TIME trial was excluded, and the primary composite outcome showed a non-significant result with the exclusion of 4 trials (IN-TIME, RESULT, TELECART, TRUST).

There was a marginal direct relationship between the primary composite outcome and atrial fibrillation and New York Heart Association functional class II in meta-regression analyses. There was potential publication bias for the primary composite outcome.

Limitations of the study include 2 studies enrolled some patients without HF and potential treatment modifiers were not evaluated.

“Multiparameter-guided strategy grants a reduction of the composite endpoint of all-cause death and HF hospitalizations, driven by a benefit in both individual components,” the study authors wrote. “Further studies are needed to test the cost-effectiveness of implant-based remote monitoring in guiding the management of HF patients, potentially legitimizing a wide application of such strategy.”

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The phase 3 study evaluated the effects of semaglutide 2.4mg administered subcutaneously once weekly on symptoms, physical function, and body weight compared with placebo in patients with symptomatic HFpEF (ejection fraction ≥45%) and obesity (BMI ≥30kg/m²) (N=529).

The co-primary endpoints of the study were the change in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and the change in body weight, from baseline to week 52. The KCCQ-CSS ranges from 0 to 100 with higher scores indicating fewer symptoms and physical limitations.

Findings showed a mean change in the KCCQ-CSS of 16.6 points with semaglutide and 8.7 points with placebo (estimated treatment difference, 7.8 points [95% CI, 4.8-10.9]; P <.001). In the semaglutide group, the mean change in body weight was -13.3% vs -2.6% in the placebo group (estimated treatment difference, -10.7 percentage points [95% CI, -11.9, -9.4]; P <.001).

The study also assessed 6-minute walking distance (6MWD) and change in C-reactive protein (CRP) as secondary endpoints. The mean increase in 6MWD was 21.5 meters with semaglutide vs 1.2 meters with placebo (estimated treatment difference, 20.3 meters [95% CI, 8.6-32.1]; P <.001). The change in CRP level was reported to be -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0.61 [95% CI, 0.51-0.72]; P <.001).

An analysis of a hierarchical composite endpoint (ie, death, heart failure events, change in KCCQ-CSS and 6MWD) showed that “semaglutide produced more wins than placebo” (win ratio, 1.72; 95% CI, 1.37-2.15; P<0.001).

The safety profile of semaglutide 2.4mg was consistent with what has been previously reported in other clinical trials. Serious side effects were reported in 13.3% of semaglutide-treated patients and 26.7% of patients who received placebo.

“We are delighted with the results from STEP HFpEF, which show that semaglutide 2.4mg is able to ease the disease burden for people with HFpEF and obesity in a substantial way,” said Martin Lange, executive vice president and head of Development at Novo Nordisk. “These results come just weeks after the topline findings of our semaglutide 2.4mg and cardiovascular outcomes trial were announced and reinforce the potential of semaglutide 2.4mg to enhance cardiovascular care, beyond weight management. We look forward to working closely with the clinical community and regulators to help realize this potential over the coming months.”

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Robert J. Mentz, M.D., from Duke University in Durham, North Carolina, and colleagues randomly assigned (1:1) 3,065 ambulatory patients with heart failure, a left ventricular ejection fraction of ≤40 percent, and iron deficiency to receive intravenous ferric carboxymaltose or placebo every six months as needed, in addition to standard therapy for heart failure. The primary outcome was a hierarchical composite of three outcomes: death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to six months in the six-minute walk distance.

The researchers found that for the primary outcome, death by month 12 occurred in 8.6 percent of patients receiving ferric carboxymaltose versus 10.3 percent receiving placebo, the ferric carboxymaltose group had 297 hospitalizations for heart failure by month 12 versus 332 in the placebo group, and the mean change from baseline to six months in the six-minute walk distance was 8 m and 4 m, respectively. The difference between the ferric carboxymaltose and placebo groups did not meet the prespecified significance level of 0.01 required for regulatory success (P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23) for the hierarchical composite of the three outcomes. For the majority of patients, repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile. A similar number of patients in each group had serious adverse events during the treatment period (27.0 percent in the ferric carboxymaltose group versus 26.2 percent in the placebo group).

“Future analyses — preferably a meta-analysis of individual-patient data from all intravenous iron trials — should assess the importance of the transferrin saturation value at baseline,” write Pieter Martens, M.D., Ph.D., and Wilfried Mullens, M.D., Ph.D., both from Hasselt University in Belgium, in an accompanying editorial. “This could help redefine the definition of iron deficiency in patients with heart failure and, we hope, help clinicians determine which patients might benefit from intravenous iron supplementation.”

Mentz reports financial ties to the pharmaceutical industry, including American Regent, a Daiichi Sankyo Group company, which funded the study.

Abstract/Full Text (subscription or payment may be required)

Editorial (subscription or payment may be required)

The post ESC: Treating Iron Deficiency May Not Aid Heart Failure Patients appeared first on The Cardiology Advisor.

Investigators sought to determine the rate of stroke in patients with HFpEF and to validate a stroke prediction model in patients with HFpEF without AF using pooled data from the I-Preserve (ClinicalTrials.gov Identifier: NCT00095238) and PARAGON-HF (ClinicalTrials.gov Identifier: NCT01920711) trials.

The researchers applied a previously validated risk model for stroke that included history of a previous stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide measurement at baseline.

A total of 3798 patients (42.6%) with AF and 5126 patients without AF were included in the pooled dataset. The patients without AF had a mean age of 70.9±7.8 years, and 58.4% were women. Among the patients with AF, the median follow-up was 3.1 years and 5.4% had a stroke (17.2 per 1000 patient-years).

For patients without AF, the median follow-up was 3.6 years and 3.7% had a stroke (10.5 per 1000 patient-years). The 1-, 2-, and 3-year cumulative incidence function (CIF) stroke rates were 1.1% (95% CI, 0.8%-1.4%), 2.0% (95% CI, 1.7%-2.5%), and 2.9% (95% CI, 2.5%-3.5%), respectively.

In the highest tertile, the 1-, 2- and 3-year CIF rates of stroke were 1.8% (95% CI, 1.3%-2.6%), 3.4% (95% CI, 2.6%-4.5%), and 4.6% (95% CI, 3.7%-5.8%), respectively. In risk tertile 3, patients had a stroke rate of 17.7 per 1000 patient-years.

According to Cox proportional hazard models, stroke risk increased as the risk score increased: tertile 2 (hazard ratio [HR], 1.78; 95% CI, 1.17-2.71); tertile 3 (HR, 3.03; 95% CI, 2.06-4.47), with tertile 1 as a reference.

The observed and predicted stroke probabilities at 1, 2, and 3 years were compared among patients divided by tertiles and were acceptable. Model discrimination was good, with an overall C index of 0.81 (95% CI, 0.68-0.91). The S₂I₂N_0-3 score discrimination for stroke also was good, with an overall C index of 0.86 (95% CI, 0.73-0.95).

Among the patients without AF who had stroke, compared with those who had no stroke, the risk of death increased markedly. The all-cause mortality rate was 4.0 (95% CI, 3.7-4.3) per 100 patient-years in patients with no stroke compared with 27.8 (95% CI, 22.1-35.0) per 100 patient-years in patients after a stroke, for an HR of 6.90 (95% CI, 5.32-8.95).

Among several limitations, the 2 large clinical trials used in the analyses had specific inclusion/exclusion criteria and likely included patients with a lower risk than occurs in the real world. Also, the investigators do not distinguish between type 1 and type 2 diabetes, although most patients with HFpEF have type 2 diabetes. In addition, ischemic and hemorrhagic stroke are not differentiated.

“…we confirmed that patients with HFpEF can have a substantial risk of stroke even in the absence of AF and validated a risk model for stroke in patients with HFpEF without AF,” wrote the researchers. “The balance of risk-to-benefit in these individuals may justify the use of prophylactic anticoagulation. This hypothesis needs to be evaluated in a prospective randomized controlled trial.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Investigators sought to assess if obvious thresholds in patient characteristics at baseline and inflection points for clinical outcomes during follow-up exist for LVEF among participants with HF, considering high-normal (supranormal) levels of LVEF and including differences according to sex.

They conducted an analysis with pooled data assessing HF from more than 33,000 participants enrolled in 6 randomized controlled trials that included patients with preserved and reduced EF. The pooled cohort median follow-up duration was 35.4 months. The investigators used Poisson regression models to assess the relationship between the incidence of all-cause mortality and HF hospitalization and LVEF.

Mean (SD) LVEF in women was 47.6% (16.5%) and 36.8% (14.2%) in men. Mean age ranged from 61.6 to 69.4 years among patients with LVEF of less than 50% and between 71.2 and 71.8 years among patients with LVEF of greater than 50% (mean 10-year age difference between patients with LVEF ≤20% vs LVEF >70%, 62 vs 72 years). Patients with LVEF of less than 50% were predominantly men (ranging 62.2% to 80.7%) and patients with LVEF of greater than 50% were predominantly women (range, 52.2% to 68.9%). Most patients were White in all LVEF categories, increasing from 67.1% (lowest LVEF category) to 84.4% (highest LVEF category).

Estimated glomerular filtration rate, ischemic pathogenesis, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) decreased as LVEF increased. Additionally, the prevalence of atrial fibrillation and diabetes, systolic blood pressure, body mass index, age, and the proportion of women increased as LVEF increased. The investigators noted no meaningful changes in characteristics as LVEF increased beyond 50% except the proportion of women continued to increase, and NT-proBNP and ischemic pathogenesis continued to decrease. As LVEF increased, comorbidities such as hypertension, diabetes, and cancer increased, while myocardial infarction, previous percutaneous catheter intervention, and coronary artery bypass graft decreased (greatest differences in hypertension and myocardial infarction, most significant in the 40% to 50% LVEF range).

As LVEF increased, (other than non-cardiovascular death) incidence of clinical outcomes decreased (LVEF inflection point about 35% for HF hospitalization; about 40% for pump failure death; about 50% for all-cause mortality and cardiovascular death). Incidence rates had insignificant further decline beyond these thresholds.

There was no evidence that patients with supranormal LVEF faced worse outcomes or of a J-shaped relationship between LVEF and death. According to available echocardiographic data, patients with supranormal LVEF had no structural differences suggestive of amyloidosis (supported by NT-proBNP levels).

Study limitations include lack of generalizability to the general population with HF, and thresholds and inflection points are not accurately defined by a statistically established method.

“Current left ventricular ejection fraction thresholds defining heart failure phenotypes are supported by this analysis of clinical outcomes,” the study authors wrote. “Incidence rates for most clinical outcomes decreased as left ventricular ejection fraction increased to a threshold of around 40% to 50% but did not change much thereafter.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The cross-sectional study assessed the effects of noncardiac comorbidities on exercise capacity and functional status in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection (HFpEF) using data from 5 clinical trials (HF-ACTION, IRONOUT-HF, NEAT-HFpEF, RELAX-HFpEF, and INDIE-HFpEF).

Exercise capacity was evaluated with peak Vo₂ and 6-minute walking test distance (6MWT), and functional status was assessed with use of the Kansas City Cardiomyopathy Questionnaire (KCCQ).

The analysis included 2777 patients (mean age, 60.3±12.8 years; 67.6% men) with HF, of whom 85% had HFrEF.

Obesity, chronic kidney disease (CKD), diabetes, chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), and anemia were independently negatively associated with peak Vo₂ and 6MWT. Multivariable analysis showed that obesity, followed by diabetes and CKD, had the strongest negative association with peak Vo₂ and 6MWT. Depression, obesity, CKD, stroke, and COPD were associated with a decrease in KCCQ.

The association between noncardiac comorbidities and exercise capacity revealed significant differences between HFrEF and HFpEF for obesity, CKD, and PVD, with all 3 showing a greater limiting effect on peak Vo₂ in patients with HFpEF (P_interaction <.05). Regarding the 6MWT, a similar finding occurred for obesity but not for CKD and PVD. No interaction of noncardiac comorbidities occurred between HFrEF and HFpEF regarding KCCQ.

The cohort had a median cumulative noncardiac comorbidity burden of 3 (IQR, 2-4), and less than 5% of patients had no comorbidities. Patients with HFpEF had a greater median noncardiac comorbidity burden vs those with HFrEF (median, 3 [IQR, 2-4] vs 2 [IQR, 1-3]; P <.001).

The participants with HFpEF had a lower 6MWT and KCCQ score, and peak Vo₂ was not different (P =.068). Each increase in additional noncardiac comorbidity was associated with a comparable progressive decrease in peak Vo₂ and KCCQ, although a more pronounced effect on 6MWT was observed in patients with HFpEF (burden HF type P_interaction =.007).

In the cluster analysis, cluster 3, which included the highest proportion of diabetes and obesity and the lowest proportion of PVD and cancer, had the worst exercise capacity and functional status.

Cox proportional hazards survival analysis adjusted for age, sex, race, and HF type with cluster 1 (highest burden of stroke and cancer) as reference, showed that cluster 2 (oldest patients and the highest proportion of CKD, PVD, and hyperlipidemia) had a 1.60 times increased risk of all-cause mortality (hazard ratio [HR], 1.60; 95% CI, 1.25-2.04; P <.001). The risk in cluster 3 was not significantly different vs cluster 1 (HR, 1.29; 95% CI, 0.97-1.70; P =.076). Each increase in comorbidity was associated with a 1.16 times higher risk of all-cause mortality (HR, 1.16; 95% CI, 1.08-1.26; P <.001) after adjustment for the same variables.

Limitations include the fact that unmeasured covariates may have affected the association between the noncardiac comorbidities and outcome variables. Also, the researchers do not account for the impact or treatment interaction of various drug interventions tested in the different clinical studies.

“Given the common use of KCCQ, 6MWT, and peak Vo₂ as endpoints in randomized controlled trials, knowledge about the importance of NCCs [noncardiac comorbidities] for certain endpoints could allow for better predefined covariate adjustment of trial endpoints,” wrote the investigators.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The retrospective cohort study evaluated the proportion of patients who had LVEF improvement after up-titration in HF medications, as well as baseline characteristics and echocardiographic parameters associated with improved LVEF in an outpatient HFrEF population.

The participants were referred to an outpatient HF clinic in Denmark from 2005 to 2013. They had an HFrEF diagnosis with an LVEF of 45% or less as evaluated by a clinician and received angiography to assess coronary status.

The participants were stratified into 4 groups based on absolute LVEF change (<0%, 0%-10%, 10%-20%, or >20%). Multivariable logistic regression was used to assess parameters associated with a major increase in LVEF of more than 20%.

A total of 686 patients (mean age, 65.3±11.3 years; 73.2% men) were included. Their median time from baseline to follow-up echocardiography was 1.3 years (IQR, 0.6-3.5 years).

The participants generally had improved systolic function with an increase in mean LVEF from 27.3 ± 9.1% at baseline to 36.3 ± 1.2% (P <.001) at follow-up. No improvement in systolic function (‍∆LVEF <0%) occurred in 127 patients. A small increase in LVEF (‍∆LVEF 0%-10%) was observed in 241 patients and 218 patients had a moderate increase in LVEF (‍∆LVEF 10%-20%). There were 100 patients who had major LVEF improvement (‍∆LVEF >20%).

Crude logistic regression showed that heart rate, body mass index, atrial fibrillation/flutter, sex, angina pectoris, ischemic cardiomyopathy, diabetes mellitus, GLS, left ventricular internal dimension in diastole (LVIDd), left ventricular mass index, and left atrial volume index were significantly associated with LVEF improvement of more than 20%.

The fully adjusted multivariable logistic regression model demonstrated a 36% increased odds of improving more than 20% of LVEF per percentage increase in absolute GLS at baseline (odds ratio [OR], 1.36; 95% CI, 1.08-1.71; P =.008). An increasing LVIDd level (OR, 0.7 per cm; 95% CI, 0.15-0.88; P =.024) was significantly associated with decreasing odds of improving more than 20% LVEF in the same model.

For the survival analysis, 73.2% of patients had follow-up available, of whom 12.9% died after a median follow-up of 2.5 years (IQR, 1.1-3.9 years). The overall mortality incidence rate was 5.0 per 100 person-years (95% CI, 3.9-6.3) and varied based on LVEF improvement (‍∆LVEF <0% vs ∆LVEF >0%, 8.3 vs 4.3 per 100 person years, P =.012).

The mortality risk decreased with increasing tertiles of LVEF improvement, as the risk was more than 3 times higher in patients in the lowest tertile vs those in the highest tertile in a multivariable Cox regression model (1 vs 3; hazard ratio 3.23; 95% CI, 1.39-7.51; P =.006).

Among several study limitations, selection bias and survival bias are possible, and the time from referral to the outpatient HF clinic until follow-up visits is highly heterogenous. Also, not all patients have a comprehensive echocardiographic examination or detailed etiology, biomarkers, or New York Heart Association classification, and the data reflect HF treatment until 2013.

“These results underline the potential of risk stratification of patients with HF, as differences in etiology, comorbidities, and heart structure and function may be correlated with HF prognosis and mortality,” wrote the researchers. “Patients with accumulated risk factors for a poor prognosis might benefit from more aggressive treatment and closer surveillance.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Data for this study were sourced from the multicenter, double-blind, randomized, active-controlled trials PARAGLIDE-HF (ClinicalTrials.gov Identifier: NCT03988634) and PARAGON-HF (ClinicalTrials.gov Identifier: NCT01920711).

Patients with HF with mildly reduced or preserved ejection fraction, defined as a left ventricular ejection fraction (LVEF) of greater than 40% (PARAGLIDE-HF) or 45% or greater (PARAGON-HF) were randomly assigned to receive sacubitril/valsartan (n=541) or valsartan (n=547) within 30 days of a worsening HF event.

The primary outcome for this prespecified analysis was the composite event of initial and recurrent HF hospitalizations, emergency department visits, and CV mortality.

The sacubitril/valsartan and valsartan recipients were aged mean 70.5 (SD, 10.4) and 71.2 (SD, 10.2) years, 48.4% and 45.9% were men, 77.8% and 79.2% were White, had a mean LVEF of 56.6% (SD, 8.1%) and 56.1% (SD, 8.0%), 97.8% and 99.1% used loop diuretics, 83.5% and 83.0% used angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and 81.5% and 79.0% used beta-blockers, respectively.

The sacubitril/valsartan cohort was associated with a lower rate of the primary composite outcome (mean, 27.5 events per 100 patient-years [PY]) compared with the valsartan monotherapy group (mean, 34.5 events per 100 PY), indicating a significant reduction (rate ratio [RR], 0.78; 95% CI, 0.61-0.99; P =.042) among total worsening HF events and CV mortality.

In addition, the dual therapy regimen was associated with a significant reduction in total HF hospitalizations and CV mortality (RR, 0.76; 95% CI, 0.60-0.97; P =.029) and worsening renal function (RR, 0.71; 95% CI, 0.54-0.94; P =.017) compared with the monotherapy regimen.

Among the entire PARAGLIDE-HF and PARAGON-HF populations, not just those randomly assigned within 30 days of a worsening HF event, sacubitril/valsartan (n=2640) was favored over valsartan (n=2622) for reducing risk for the primary composite outcome (RR, 0.86; 95% CI, 0.75-0.98; P =.027); the composite of total HF hospitalizations and CV mortality (RR, 0.87; 95% CI, 0.76-0.99; P =.040); the composite of 50% decline or greater in estimated glomerular filtration rate, end-stage renal disease, or renal mortality (hazard ratio [HR], 0.60; 95% CI, 0.44-0.83; P =.002); and worsening renal function (odds ratio [OR], 0.72; 95% CI, 0.63-0.82; P <.001).

However, dual therapy was associated with increased risk for symptomatic hypotension compared with monotherapy (OR, 1.50; 95% CI, 1.31-1.72; P <.001).

In subgroup analyses, no significant group interactions were observed. However, when stratified by LVEF, dual therapy had a significant effect for reducing the primary outcome among patients with LVEF of 60% or less in the primary analysis group (RR, 0.70) or full cohort (RR, 0.78), but no significant effect was observed for those with higher LVEF (RR range, 1.04-1.09).

This analysis was limited by differences among the included parent studies, missing patient-reported outcome measures for certain endpoints, and reliance on investigator-reported data regarding renal mortality.

The study authors concluded, “These pre-specified pooled analyses of PARAGON-HF and PARAGLIDE-HF including over 5,000 participants worldwide strengthen the current evidence base supporting the use of sacubitril/valsartan in patients with HF with mildly reduced or preserved ejection fraction, especially among those with an LVEF below normal, and irrespective of care setting.”

Disclosures: This research was supported by Novartis Pharmaceuticals Corporation. One or more study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Sleep-disordered breathing is common among patients with HFrEF and investigators from the medXcloud group hypothesized that among these patients, adherence to PAP therapy would be associated with reduced health care utilization.

To test their hypothesis, they conducted this retrospective, observational study using data from deidentified administrative claims collected by more than 100 health care plans in the United States. Patients (N=3182) with HFrEF who received a new diagnosis of OSA between 2014 and 2019 were evaluated for healthcare utilization on the basis of adherence to PAP therapy. Treatment adherence was objectively measured by PAP devices during the first year of use and patient compliance was defined as use for 4 or more hours per night on 70% of nights over 30 consecutive days in a 90-day period. Adherence was defined as compliance in all 4 quarters in the first year, intermediate adherence as compliance in 1 to 3 quarters in the first year, and nonadherence as noncompliance in all quarters in the first year. To balance for cohort differences, adherent and nonadherent patients were matched in a 1:1 ratio.

The patients had a mean age of 59.7 (SD, 11.2) years, 30.1% were women, 39.0% were morbidly obese, 27.3% had an implanted cardiac device, 80.1% were using beta-blockers, 64.9% were using diuretics, and 5.6 (SD, 2.3) had comorbid conditions.

In the first quarter of device use, 63.2% were compliant to treatment and during the first year of treatment, 39% were adherent. Predictors for PAP adherence included older age, atrial fibrillation, and adherence to beta-blockers.

Among a subset of 738 adherent and 738 nonadherent patients, the treatment adherent group had higher rates of PAP use with regards to hours per day (mean, 6.6 vs 0.4; P <.001), days per week (mean, 6.6 vs 0.9; P <.001), and hours per use per day (mean, 7.0 vs 2.9; P <.001) compared with the nonadherent group.

The composite outcome of health care resource utilization in the first year of PAP use was significantly lower among the PAP adherent group compared with the nonadherent group (mean, 0.92 vs 1.15 visits; P =.006). Stratified by type of visit, PAP adherence associated with fewer emergency department (ED) visits (mean, 0.64 vs 0.81; P =.005) but not fewer all-cause (mean, 0.28 vs 0.34; P =.140) or cardiovascular (mean, 0.09 vs 0.11; P =.409) hospitalizations compared with nonadherence.

Among all patients, PAP adherence associated with fewer ED visits than nonadherence (P <.001) and with fewer ED visits (P =.002) and all-cause hospitalizations (P =.049) compared with intermediate adherence.

“These data provide additional real-world evidence for the role of PAP therapy in reducing health care resource use. Therefore, assessment of OSA in patients with heart failure should be encouraged until more definitive outcomes data emerge,” wrote the study authors.

Disclosures: This research was supported by ResMed. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Ming-Shyan Lin, from Chang Gung Memorial Hospital Chiayi Branch in Taiwan, and colleagues conducted a retrospective cohort study between 2001 and 2021 involving ADHF patients discharged from hospitals. The primary outcome components were cardiovascular mortality and heart failure rehospitalizations, as well as all-cause mortality, acute myocardial infarction (AMI), and stroke.

A total of 12,852 ADHF patients were identified, including 17.3 percent with heart failure with mildly reduced ejection fraction (HFmrEF). The researchers found that patients with HFmrEF had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease in comparison with patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Similar rates of cardioversion and coronary interventions were seen for both HFmrEF and HFrEF. An intermediate clinical outcome was seen between HFpEF and HFrEF; the highest rate of AMI was seen with HFmrEF (9.3, 13.6, and 9.9 percent for HFpEF, HFmrEF, and HFrEF, respectively). The AMI rates were significantly higher in HFmrEF than HFpEF but not HFrEF.

“These findings are of importance to future research strategies on prevention and treatment of different HF types and ischemic heart disease,” the authors write.

Abstract/Full Text

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Researchers included 7539 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD; ClinicalTrials.gov Identifier: NCT00000620) study who had completed 4 years of follow-up or experienced a HF event during that period, had at least 3 recorded estimated glomerular filtration rate (eGFR) values, and available albumin-to-creatinine ratio (UACR) data. The team estimated associations between rapid kidney function decline and odds of HF, which was defined as death or hospitalization due to HF. Study participants completed questionnaires to provide demographic information, diabetes duration, smoking status, and medical and history.

During the 4-year follow-up duration, 1573 participants (20.9%) experienced rapid kidney function decline and 255 individuals (3.4%) had a HF event, according to the report. Regardless of cardiovascular disease history, rapid kidney function increased the risk of HF (odds ratio [OR], 3.23; 95% CI, 2.51–4.16; P <.0001).

Patients with a HF episode had a significantly more negative change in eGFR compared with participants without HF (median −3.9 vs −1.6 ml/min/1.73m²/year; P =.0002), which resulted in a higher rapid kidney function prevalence at follow-up (45% vs. 20%; P <.0001). Participants with a baseline eGFR less than 60 mL/min/1.73 m², increased baseline UACR, and rapid kidney function decline experienced an approximate 15-fold HF risk compared with individuals without these risk factors (OR, 14.53; 95% CI, 6.28-33.62). Adjusting for eGFR and UACR at baseline did not alter the association between rapid kidney decline and HF risk (OR 3.74; 95% CI, 2.63-5.31), the report shows.

Study limitations include a failure to consider treatment with glucose-lowering drugs developed after 2009 and an inability to generalize these findings for individuals with diabetes and lower cardiovascular risk.   

“Using rapid kidney function decline may help the early identification patients who could especially benefit from preventing treatment such as SGLT2 inhibitors …,” according to the study authors.

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IVRT, isovolumic contraction time (IVCT), left ventricular ejection time (LVET), and the myocardial performance index (MPI; defined as IVCT+IVRT/LVET) represent the cardiac time intervals. Investigators assessed whether normal aging includes longitudinal changes in cardiac time intervals among a heart-healthy population.

Secondary aims included identification of risk factors for cardiac time interval acceleration and to determine whether an increased risk for incident HF is associated with longitudinal changes in these time intervals.

Investigators conducted a longitudinal cross-sectional analysis of the 4^th and 5^th Copenhagen City Heart Study (CCHS4 and CCHS5, respectively; ClinicalTrials.gov Identifier: NCT02993172 ), designed as a prospective cohort study to identify cardiovascular risk factors among participants from the general population in Denmark. Patients from the original study who underwent echocardiographic examination with color tissue Doppler imaging were included in the analysis.  

Incident HF was the primary endpoint and all-cause death the competing event, with study examinations performed 10.5 years apart. Multivariable linear regression was used to assess the impact of clinical and nonclinical factors on changes in cardiac time intervals.

Investigators found a significant increase over time in IVRT (12±22 ms), IVCT (5±15 ms), LVET (2±29 ms), and consequently MPI (0.05±0.12).

An increase in IVRT was associated with male sex (P =.044), smoking (P =0.006), diastolic blood pressure (P =0.030), and age (P <.001). Impact of age on change in IVRT was marked until about 60 years.

An IVRT decrease was accelerated by higher levels of hemoglobin A1c (P =.039). Increase in IVCT was not accelerated by any of the clinical factors explored in this study.  

An accelerated decrease in LVET was associated with systolic blood pressure (P =.043) and male sex (P =.020).

Among participants aged less than 65 years, an increased risk for subsequent HF was associated with increasing IVRT over a 10-year period (per 10 ms increase, P =.034).

Smoking (P =.011), higher diastolic blood pressure (P =.020), male sex (P =.021), and more advanced age (P =.001) were noted as accelerators of an increase in MPI.

Study limitations included use of different ultrasound machines and postprocessing software versions to perform echocardiographic examinations during CCHS4 and CCHS5, lack of antihypertensive medication data, and low numbers of cardiac events.

“It is of clinical importance to identify the risk factors that accelerate changes of the cardiac time intervals. This could potentially guide risk factor modification and improve the understanding of the aging heart assessed by the cardiac time intervals,” study authors stated.

Disclosure: At least one study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The population-based, observational, matched cohort study evaluated the association between pregnancy complicated by pregnancy-induced hypertensive disorders in primiparous women and risk for ischemic and nonischemic HF.

The Medical Birth Register in Sweden was used to identify primiparous women who gave birth from 1988 through 2019. The participants with hypertensive disorder of pregnancy were individually matched with up to 5 comparator patients according to maternal age at delivery and year of delivery. The matched comparators did not have hypertensive disorder during the index pregnancy.

The follow-up ended at the outcome, death from cause other than HF, first migration from Sweden, or the study end date of December 31, 2020, whichever came first.

A total of 79,334 women with pregnancy-induced hypertension were matched with 396,531 women with a normotensive pregnancy. The median follow-up was 13.2 (IQR, 6.1-22.0) years (exposed to hypertension, 13.2 [IQR, 6.2-22.0] years; unexposed, 13.1 [IQR, 6.1-22.0] years).

The women with pregnancy-induced hypertensive disorder had an incidence rate of overall HF of 3.3 per 10,000 person-years, compared with 1.8 per 10,000 person-years in the matched normotensive comparator patients (crude hazard ratio [cHR], 1.81 [95% CI, 1.61-2.04]; adjusted HR [aHR], 1.70 [95% CI, 1.51-1.91]).

Incident nonischemic HF occurred in 290 (0.5%; 2.6 per 10,000 person-years) women with pregnancy-induced hypertensive disorder vs 869 (0.2%; 1.5 per 10,000 person-years) in the comparator group during follow-up, for an increased rate of about 60% of nonischemic HF after pregnancy-induced hypertensive disorder (cHR, 1.67 [95% CI, 1.47-1.91]; aHR, 1.60 [95% CI, 1.40-1.83]). In addition, 88 (0.1%; 0.8 per 10,000 person-years) women with pregnancy-induced hypertensive disorder and 168 (0.04%; 0.3 per 10,000 person-years) of matched normotensive women had ischemic HF (cHR, 2.59 [95% CI, 2.00-3.36]; aHR, 2.08 [95% CI, 1.44-3.00]).

Preterm delivery occurring prior to gestational week 34 was associated with a 2.5-fold increased rate of any HF (cHR, 2.46 [95% CI, 1.82-3.32]), a 2.3-fold increased rate of nonischemic HF (cHR, 2.33 [95% CI, 1.65-3.31]), and a 3.6-fold increased rate of ischemic HF (cHR, 3.64 [95% CI, 1.97-6.74]).

The incidence rates were greatest within 6 years after a hypertensive index pregnancy (any HF: cHR, 2.09 [95% CI, 1.52-2.89]; nonischemic HF: cHR, 1.86 [95% CI, 1.32-2.61]; and ischemic HF: cHR: 6.52 [95% CI, 2.00-12.34]). The rates decreased slightly afterward but were still significantly increased during all time periods.

The researchers noted that women with a history of pregnancy-induced hypertensive disorder may have an increased prevalence of subclinical ischemic heart disease, including coronary artery calcification, which could have resulted in an underestimation of the risk for ischemic HF and overestimation of the risk for nonischemic HF. Also, residual confounding is possible, and the study had limited power in some of the stratified and adjusted analyses. Furthermore, the findings are based on demographic characteristics of the Swedish population and health care settings.

“Primiparous women without a history of CVD and pregnancy-induced hypertensive disorder are at increased short-term and long-term risk of nonischemic and ischemic heart failure,” the study authors wrote.

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The retrospective cohort study assessed cardiac surveillance per established guideline recommendations in a real-world clinical setting with use of electronic health records data from the OneFlorida Clinical Research Consortium.

Researchers identified patients diagnosed with cancer who received treatment from January 1, 2012, until April 30, 2020. Eligible patients were prescribed 2 or more doses of an anthracycline, including doxorubicin, daunorubicin, epirubicin, idarubicin, and mitoxantrone.

The primary objective was to evaluate associations between racial and ethnic groups in cardiac surveillance among cancer survivors after exposure to anthracyclines.

The cohort included 5430 patients and their median age was 53 years (63% women). Among the participants, 47% were non-Hispanic White, 31% were Hispanic, 17% were non-Hispanic Black, and 5% were classified as other. The most common cancer diagnoses associated with anthracycline therapy included lymphoma (35.6%), breast cancer (30.5%), and sarcoma (25.4%).

Of these patients, 63% received baseline imaging with echocardiography. Non-Hispanic Black patients were significantly less likely to have received a cardiac imaging assessment at baseline (odds ratio [OR], 0.75; 95% CI, 0.63-0.88; P =.0006) compared with non-Hispanic White patients. No significant differences were found for Hispanic or Non-Hispanic Black patients vs non-Hispanic White patients at 6 months and 12 months.

B-type natriuretic peptide (BNP) and N-terminal (NT)-proBNP assessment at baseline occurred in 6% of the patients with cancer, 7.7% in non-Hispanic White patients, 6.5% in non-Hispanic Black patients, 3.6% in Hispanic patients, and 4.3% patients classified as other. Hispanic patients had significantly reduced rates of BNP and NT-proBNP assessments at baseline, 6 months, and 12 months.

Regarding any cardiac surveillance (echocardiogram, BNP/NT-proBNP), non-Hispanic Black patients had a lower rate of baseline assessment than non-Hispanic White patients (63.3% vs 60%) with an adjusted OR of 0.76 (95% CI, 0.64-0.89; P =.001). No differences were observed in these 2 groups at 6 and 12 months. Hispanic patients had a lower rate of cardiac surveillance at 6 and 12 months compared with non-Hispanic White patients.

In adjusted ORs for age, sex, year of chemotherapy, diabetes, obesity, hypertension, and hyperlipidemia, compared with non-Hispanic White patients, Hispanic patients had a significantly lower rate of cardiac surveillance at 6 months (OR, 0.84; 95% CI, 0.72-0.98; P =.025) and 12 months (OR, 0.85; 95% CI, 0.74-0.98; P =.027).

Study limitations include lack of analysis for anthracycline dosing or radiation intensity. Other limitations include missing laboratory data, so it is not possible to assess changes in biomarkers for cardiotoxicities such as BNP, NT-pro BNP, or cardiac troponin for each racial or ethnic group.

“Recognition and clinical evaluation of heart failure risk factors such as hypertension, diabetes, and obesity should occur before anthracycline initiation,” wrote the investigators. “Clinicians need to be cognizant of social inequities and initiate efforts to ensure recommended cardiac assessment and active surveillance occurs in patients receiving anthracyclines.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Investigators aimed to explore the relationship between HF hospitalization and death in patients with HFmrEF or HFpEF receiving beta-blockers. They conducted a propensity score-adjusted real-world observational cohort study that included 435,897 older outpatients (≥65 years of age) in the United States (US) with HF and EF of 40% or greater. Data were deidentified and from the US PINNACLE Registry between 2013 and 2017. The investigators used multivariable Cox regression models to evaluate the associations between beta-blocker use and death, HF hospitalization, and the composite of death and HF hospitalization.

Among all included patients (HFpEF, 360,223; HFmrEF, 75,674) there were 289,377 patients (age, 76.2±7.8 years; 52.6% men; 71.9% White; 5.5% Black) using a beta-blocker at first encounter, although this was less common among patients with HFpEF vs HFmrEF (64.0% vs 77.7%; P <.001). There were 146,520 patients not using a beta-blocker at first encounter (age, 76.0±7.8 years; 50.5% men; 73.2% White; 5.1% Black). Of the patients receiving beta-blocker therapy, 70.8% had coronary artery disease, 86.2% had hypertension, 30.3% had diabetes mellitus, 45.6% had atrial fibrillation/flutter, 2.8±1.2 were receiving antihypertensive medications, and 72.7% were receiving a statin.

The investigators subsequently excluded 29,894 patients with nonoverlapping propensity scores. Except for sex, prior coronary artery bypass surgery, number of antihypertensive medications, use of statin, systolic blood pressure, prior percutaneous coronary intervention, and coronary artery disease, all other standardized differences were less than 10%.

In adjusted models, there were significant interactions between beta-blocker therapy and left ventricular ejection fraction (LVEF) for death, HF hospitalization, and the composite of death/HF hospitalization (all P <.001). As EF increased, the risk related to beta-blocker use increased, although in patients with HFmrEF, beta-blockers were associated with decreased risk of death and HF hospitalization.

There was a higher risk of HF hospitalization and lack of survival benefit in patients with HFpEF (≥40%), noticeably in patients with EF of greater than 60%. They found no significant 3-way interactions between beta-blocker use, LVEF, and hypertension (P_interaction =.97; P =.51), atrial fibrillation (P_interaction =.17; P =.60), or myocardial infarction (P_interaction =.18; P =.18).

Study limitations include a lack of confirmatory randomized data, as well as inclusion of only patients that were aged at least 65 years. Additionally, cause of death was not discernable by investigators.

“In a large, real-world, propensity score-adjusted cohort of older patients with HF and LVEF 40% or greater, beta-blockers were associated with a higher risk of HF hospitalization as LVEF increased,” the investigators concluded. “There was evidence of potential benefit for HF hospitalization and death in patients with HFmrEF, but in patients with higher LVEF (particularly >60%), there was a lack of survival benefit and a higher risk of HF hospitalization associated with the use of beta-blockers.” Due to the potentially higher risk of adverse outcomes in patients with HFpEF, the investigators urge careful consideration in the use of beta-blockers in this patient population.

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Researchers hypothesized that NSAID use was prevalent in patients with T2DM and that even short-term use of NSAIDs was linked to an elevated risk of first-time HF hospitalization.

The analysis included data from Danish nationwide health registers for patients aged 18 to 100 years who were diagnosed with diabetes mellitus or initiated antidiabetic treatment in 1998 to 2021. Follow-up began 120 days after T2DM diagnosis, and the patients were followed until first-time HF hospitalization, death, or December 31, 2021, whichever came first.

The primary exposure was a claimed prescription of celecoxib, diclofenac, ibuprofen, or naproxen, and the investigators reported proportions of patients who claimed up to 4 prescriptions within 1 year from the start of follow-up. In the case-crossover analyses, the participants were considered exposed if an NSAID prescription was claimed within 28 days before the initial HF hospitalization.

The cohort included 331,189 patients diagnosed with T2DM (median age, 62 years [IQR, 52-71 years]; 44.2% women) in the study period. During the first year, 16% of patients claimed 1 or more NSAID prescriptions (ibuprofen, 12.2%; diclofenac, 3.3%; naproxen, 0.9%; celecoxib, 0.4%), and 3% claimed 3 or more prescriptions within a year.

A total of 23,308 patients were hospitalized with first-time HF during the follow-up (median age, 76 years [IQR, 68-83 years]; 39.3% women), and the median time to the event was 5.9 years (IQR, 2.6-10.2 years). With use of the case-crossover design, the association of first-time HF to previous NSAID exposure showed an increased risk. The odds ratio (OR) for risk for HF hospitalization with any NSAID in the 28-day exposure window was 1.43 (95% CI, 1.27-1.63). It was 1.41 (95% CI, 1.20-1.65) in the 14-day exposure window and 1.36 (95% CI, 1.22-1.53) in the 42-day exposure window. The associations were comparable for diclofenac and ibuprofen, and analyses for celecoxib and naproxen demonstrated statistically insignificant results, with few events available to assess.

Stronger associations with increased ORs occurred in subgroups of participants aged 65 years or older, and no association was observed in patients aged younger than 65 years. The strongest association was in participants without a previous claimed prescription of NSAIDs (OR, 2.71; 95% CI, 1.78-4.23). For patients with increased hemoglobin (Hb) A1c levels of 48 mmol/mol or higher and treated with 0 to 1 antidiabetic drug, the OR was 1.68 (95% CI, 1.00-2.88).

All-cause mortality after the initial HF hospitalization was reduced in patients exposed to NSAIDs compared with those not discordantly exposed to NSAIDs before HF hospitalization, with a 1-year standardized absolute risk difference (ARD) of -2.9% (95% CI, -5.3% to -0.4%), a 3-year ARD of -3.7% (95% CI, -6.9% to -0.5%), and a 5-year ARD of -3.9% (95% CI, -7.3% to -0.5%).

Among several limitations,misclassification may have occurred and undiagnosed ischemic heart disease or first-time ischemic heart disease between the control and index period could have introduced confounding and protopathic bias. Also, association does not imply causation, and the case-crossover design did not allow for an interpretable stratification of NSAID dosage.

“An elevated risk of HF was found when relating short-term NSAID use and first-time HF hospitalization using a self-controlled design with advanced age, elevated HbA_1c levels, and no previous use of NSAIDs most strongly associated with first-time HF,” the study authors wrote. “Interestingly, the prognosis following incident HF for both NSAID-exposed and nonexposed was comparable. Individual risk assessment is advised if prescribing NSAIDs for patients with T2DM.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The multicenter, retrospective, cohort registry study sought to examine the relationship between time-to-target rate of urine volume following treatment initiation and clinical outcomes during hospitalization and after discharge among patients hospitalized for ADHF from January 2011 to December 2016.

Patients treated with intravenous furosemide, oral torasemide, oral azosemide, and oral tolvaptan were included. Time-to-target rate of urine volume was defined as the time from hospitalization to a urine volume rate of 100 mL/h.

The participants were categorized into 3 groups, patients with a time-to-target rate of urine volume of less than 24 hours (n=248; day 1 group), patients with a time-to-target rate of urine volume of 24 to 72 hours (n=172; days 2 to 3 group), and patients with a time-to-target rate of urine volume of more than 72 hours or whose urine output rate did not reach 100 mL/h after admission (n=369; no-target urine volume group). The primary outcome was a 1-year composite of death or heart failure hospitalization.

The no-target urine volume group had the oldest mean age (82.3±10.6 years, P <.01) of the 3 groups, while the day 1 group had the youngest (77.6±12.7 years). Men represented 56.1% of patients in the day 1 group, 59.3% of patients in the days 2 to 3 group, and 51.2% of patients in the no-target urine volume group.

The overall in-hospital mortality rate was 4.3%. The day 1, days 2 to 3, and no-target urine volume groups had 7, 10, and 41 deaths (P =.0007), respectively. A shorter time-to-target rate of urine volume was associated with reduced in-hospital mortality. Event-free survival by time-to-target rate of urine volume was significantly greater for the day 1 group (67.7%; P =.004), compared with the days 2 to 3 (54.1%) and no-target urine volume (56.9%) groups, based on the Kaplan-Meier survival curve for the 1-year composite endpoint. After adjustment, the composite endpoint had a statistically significant association with earlier time-to-target rate of urine volume. Mortality also had a statistically significant association with earlier time-to-target rate of urine volume after adjustment for confounding factors.

No significant difference was observed in event-free survival in the 3 groups (day 1 group, 60.3%; days 2-3 group, 57.1%; no-target urine volume group, 61.1%; P =.71) when the 1-year composite endpoint was compared by time-to-target rate of urine volume (1 mL/kg/h). After adjustment, the composite endpoint was not significantly associated with time-to-target rate of urine volume (1 mL/ kg/h), and only time-to-target rate of urine volume (100 mL/h) was statistically significant for the composite endpoint in the day 1 group.

Multivariate analysis demonstrated that the negative predictors of time-to-target rate of urine volume (100 mL/h) at day 1 were age, prior hospitalization for heart failure, and N-terminal pro-brain natriuretic peptide level. Positive predictors were carperitide use (odds ratio [OR], 0.69; 95% CI, 0.48-0.99; P =.05) and early tolvaptan administration (OR, 0.60; 95% CI, 0.42-0.85; P =.004). This model had an area under the receiver operating characteristic curve of 0.64.

The researchers noted that their study is not a randomized, double-blind, placebo-controlled trial, and there are differences in baseline patient characteristics. Also, acute treatment was guideline-based but was at the discretion of the treating physician, and the association between door-to-diuretic time and prognosis was not evaluated.

“…patients with T2TUV [time-to-target rate of urine volume] (100 ml/h) of less than 24 h had lower all-cause mortality and readmission rates at 1 year and lower WRF [worsening renal function] and hospital length of stay,” the study authors wrote. “Thus, T2TUV (100 ml/h) is effective in determining the efficacy of diuretic therapy in acute heart failure.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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The aim of this study was to compare clinical, echocardiographic, and invasive hemodynamic characteristics in patients with EILAH and those with RELAH. Another objective was to determine if these groups differed in responsiveness to atrial shunt treatment.

The authors included 626 individuals from the REDUCE LAP-HF II (Study to Evaluate the Corvia Medical, Inc., IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure; ClinicalTrials.gov Identifier: NCT03088033) study.

For the primary outcome, the authors randomly assigned participants with ejection fraction at or above 40% and exercise pulmonary capillary wedge pressure (PCWP) equal to or exceeding 25 mm Hg to receive an atrial shunt or a sham procedure. The authors also compared patients with heart failure and EILAH (29%) and those with heart failure and RELAH on a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status.

The EILAH group had similar distributions across race/ethnicity, sex, and obesity levels but were slightly younger than participants in the RELAH group. EILAH group members were less likely to have chronic kidney disease, diabetes, hypertension, and current or prior atrial fibrillation.

Patients with EILAH had higher estimated glomerular filtration rates and higher use of mineralocorticoid receptor agonists. They also had lower uses of loop diuretic agents and beta-adrenergic blocking agents.

Patients with EILAH had symptoms with similar severity but had decreased natriuretic peptide levels, longer 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, lower LA volumes, lower E/e’, and better LA strain. The EILAH group also had lower PCWP at rest, but exercise increased this outcome.

In patients that received shunt therapy, the primary outcome was not statistically significant in the EILAH group (win ratio, 1.08; P =.69) or RELAH group (win ratio, 0.98; P =.85). Patients with EILAH were more likely to exhibit features associated with atrial shunt responsiveness, including peak exercise pulmonary vascular resistance of less than 1.74 WU and lack of a pacemaker (63% vs 46%; P <.001). When responder characteristics were present, the win ratio for the primary outcome was 1.56 (P =.08) in patients with EILAH, compared with 1.51 (P =.04) in those with RELAH.

According to the researchers, EILAH can be difficult to detect without the use of invasive hemodynamics testing. Alternatively, practitioners can assess symptom severity in the outcome measures analyzed in this study.

“Although they have significant impairment of quality of life, these patients appear to have a less advanced stage of myocardial and pulmonary vascular dysfunction,” the study authors wrote. “Importantly, they have a number of characteristics that suggest they may derive benefit from atrial shunt therapy. These findings merit further evaluation in prospective trials.”

Disclosure: This research was supported by Corvia Medical, Inc. Please see the original reference for a full list of authors’ disclosures.

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The occurrence of cachexia and sarcopenia in HF is associated with poorer outcomes and quality of life. To date there have been no large-scale studies evaluating the prevalence and overlap of the 2 conditions in HF.

This was a substudy of the FRAGILE-HF trial, a prospective, observational study conducted at 15 hospitals in Japan between 2016 and 2020. Inpatients (N=905) with HF were assessed for sarcopenia and cachexia by trained personnel, defined using the Asian Working Group for Sarcopenia (AWGS) criteria and as described by Evans et al, respectively. The primary endpoint of this study was all-cause mortality risk on the basis of cachexia and sarcopenia comorbidities.

The patients had neither cachexia or sarcopenia (n=504), cachexia alone (n=196) sarcopenia alone (n=105), or both cachexia and sarcopenia (n=100). The patient groups had median ages of 79 to 82 years, 49.0% to 74.3% were men, they had mean BMIs of 18.1 to 23.1, body fat mass of 22.6% to 28.5%, and median skeletal muscle indices of 5.98 to 7.57.

In general, sarcopenia associated with older age, male gender, increased C-reactive protein levels, and decreased left ventricular ejection fraction, whereas cachexia associated with atrial fibrillation and decreased hemoglobin and serum albumin levels. Patients who had co-occurring cachexia and sarcopenia had the lowest body fat percentage and BMI.

During the 2-year follow-up, 17.5% of patients died from cardiovascular (n=124) or noncardiovascular (n=34) causes. The patients with co-occurring cachexia and sarcopenia had higher mortality rates than the other groups (P <.001).

In the final model, co-occurring cachexia and sarcopenia associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR], 2.78; 95% CI, 1.80-4.29; P <.001) as well as the composite outcome of mortality and rehospitalization for HF (aHR, 1.45; 95% CI, 1.01-2.09; P =.046) compared with having neither cachexia nor sarcopenia.

Of note, all-cause mortality risk was not associated with either cachexia (hazard ratio [HR], 1.45; 95% CI, 0.96-2.18; P =.078) or sarcopenia (HR, 1.56; 95% CI, 0.94-2.57; P =.083) alone in the unadjusted models.

This study may have been limited as cachexia and sarcopenia evaluations occurred only once during index admission.

“Sarcopenia and cachexia are prevalent among older hospitalized patients; however, the overlap between the 2 is not as prominent as previously expected,” wrote the study authors.

Disclosures: This research was supported by Novartis Pharma. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Sotagliflozin is a sodium-glucose cotransporter type 2 (SGLT2) inhibitor that also inhibits SGLT1. Inhibiting SGLT2 reduces renal reabsorption of glucose and sodium, while inhibiting SGLT1 reduces intestinal absorption of glucose and sodium.

The approval was based on data from the multicenter, randomized, double-blind, placebo-controlled phase 3 SOLOIST-WHF (ClinicalTrials.gov Identifier: NCT03521934) and SCORED (ClinicalTrials.gov Identifier: NCT03315143) studies.

SOLOIST-WHF evaluated the CV efficacy of sotagliflozin in 1222 hemodynamically stable adults with type 2 diabetes who had recently been hospitalized for worsening HF (median left ventricular ejection fraction was 35%). SCORED evaluated the CV efficacy of sotagliflozin in 10,584 adults with type 2 diabetes, CKD (estimated glomerular filtration rate of 25-60mL/min/1.73m²), and additional CV risk factors (eg, history of HF, obesity, dyslipidemia, hypertension, or elevated cardiac and inflammatory biomarkers).

Patients were randomly assigned to receive sotagliflozin or placebo orally once daily, in addition to standard of care. The primary endpoint for both studies was the total occurrence (first and potentially subsequent) of CV death, hospitalization for HF, and urgent HF visits after randomization.

In both trials, sotagliflozin was superior to placebo in reducing the primary composite endpoint. In SOLOIST-WHF, the number of primary endpoint events per 100 patient-years was 51.3 in the sotagliflozin arm and 76.4 in the placebo arm (hazard ratio [HR], 0.67; 95% CI, 0.53-0.85; P =.001). In SCORED, the number of primary endpoint events per 100 patient-years was 5.6 in the sotagliflozin arm and 7.5 in the placebo arm (HR, 0.75; 95% CI, 0.63-0.88; P <.001).

The most common adverse reactions reported were urinary tract infection, volume depletion, diarrhea, and hypoglycemia.

Inpefa is supplied as 200mg and 400mg tablets in 30- and 90-count bottles. The product is expected to be available by the end of June 2023.

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Researchers presented findings from a prespecified analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure; ClinicalTrials.gov Identifier: NCT03619213) trial. DELIVER enrolled patients aged 40 years or older with HFmrEF or HFpEF, defined as HF with New York Heart Association (NYHA) functional class II to IV and an EF greater than 40%, who were randomly assigned to dapagliflozin 10 mg once daily or matching placebo.

The primary outcome was the composite of worsening HF or cardiovascular death, whichever occurred first, and the analyses assessed the predefined secondary outcomes of total worsening episodes of HF and cardiovascular deaths.

The cohort included 6263 patients (43.9% women; mean age, 71.7 [SD, 9.6] years). During a median follow-up of 2.3 (IQR, 1.7-2.8) years, 1380 nonfatal worsening HF events (urgent visits or hospital admissions) occurred in 822 patients. The patients who had 2 or more HF events had increased heart rates, body mass index, and N-terminal pro-B-type natriuretic peptide and hemoglobin A_1c levels.

The rate for total HF events and cardiovascular death was 15.3 per 100 patient-years in patients who received placebo and 11.8 per 100 patient-years in those who received dapagliflozin. The rate ratio (RR) from the Lin, Wei, Yang, and Ying (LWYY) model for total HF events and cardiovascular death was 0.77 (95% CI, 0.67-0.89; P <.001) vs a hazard ratio (HR) of 0.82 (95% CI, 0.73-0.92; P <.001) for the traditional time to first event composite of worsening HF event or cardiovascular death.

In analysis of the components of the total worsening HF events and cardiovascular deaths composite outcome, a decrease was observed in total HF events, with an RR of 0.73 (95% CI, 0.62-0.87; P <.001), but not for cardiovascular death (HR, 0.88; 95% CI, 0.74-1.05; P =.17). The joint frailty model yielded an RR of 0.72 (95% CI, 0.65-0.81; P <.001) for HF events and 0.87 (95% CI, 0.72-1.05; P =.14) for cardiovascular death.

In a post hoc analysis, the HR of subsequent death was 1.67 (95% CI, 0.90-3.12) in patients whose first event was an urgent HF visit and 5.70 (95% CI, 4.95-6.56) in those whose first event was an HF hospitalization, compared with patients with no HF event.

Dapagliflozin’s effect on total HF events and cardiovascular deaths was not different among any of the predefined subgroups. Treatment heterogeneity was not found in patients with and without an improved EF or based on whether they were randomized within 30 days of hospitalization.

Study limitations include a limited follow-up, and the findings may not apply to all patients with HFmrEF or HFpEF in the broader population. Also, hospitalization rates vary widely, and the participants were enrolled in 20 countries.

“HF events are common and preventable, and the efficacy of dapagliflozin in reducing the number of these events is consistent across a broad range of subgroups and across the spectrum of EF,” wrote the investigators.

Disclosure: The DELIVER trial was funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Jasper J. Brugts, M.D., from Erasmus MC University Medical Center in Rotterdam, Netherlands, and colleagues randomly assigned 348 patients with chronic heart failure of New York Heart Association class III and a previous heart failure hospitalization to hemodynamic monitoring (CardioMEMS-HF system) or standard care (176 and 172, respectively). The mean difference in the KCCQ overall summary score at 12 months was measured as the primary end point.

The researchers found that the between-group difference in mean change in KCCQ overall summary score at 12 months was 7.13 (+7.05 and −0.08 in the CardioMEMS and standard care groups, respectively). In the responder analysis, the odds ratios were 1.69 for an improvement of at least 5 points in the KCCQ overall summary score and 0.45 for a deterioration of at least 5 points in the CardioMEMS-HF versus standard care groups. The freedom of device-related or system-related complications was 97.7 percent and freedom of sensor failure was 98.8 percent.

“Hemodynamic monitoring and subsequent individualized modification of diuretics and guideline-directed medical therapy substantially and significantly improve quality of life and reduce the number of heart failure hospitalizations among patients with chronic heart failure,” the authors write.

Several authors disclosed ties to pharmaceutical companies, including Abbott Laboratories, which partially funded the study and developed the CardioMEMS-HF system.

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Researchers conducted a retrospective study in the US from 2001 and 2012. Data were collected from the Medical InformationMart for Intensive Care III (MIMIC-III) database. The International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes were used to identify individuals with AHF. Nutritional status was categorized based on serum albumin levels and prognostic nutritional index (PNI). Serum albumin was classified into low (<3.5 g/dL) or malnourished and high (≥3.5 g/dL) or well-nourished. PNI was categorized into high (≥38) or well-nourished and low (<38) or malnourished. Obesity or overweight status was classified based on body mass index (BMI). 

The primary study outcome was 90-day mortality.

A total of 1325 patients were enrolled in the study. The mean age was 72.4±13.1 years and52.1% of the patients being men. Of the total population, 48.7% of patients were considered well-nourished and 51.3% were considered malnourished. 

Before propensity-score matching, patients with a malnourished status demonstrated poorer clinical outcomes, including higher-in-hospital and 90-day mortality. A total of 16.5% of these patients experienced in-hospital mortality compared with 9.5% of those with a well-nourished status; and 28.7% vs 18.0%, respectively, experienced 90-day mortality (P <.001).

In addition, 90-day mortality was negatively correlated with overweight or obese status with adjusted hazard ratios (HRs) of 0.47 (95% CI, 0.30-0.74; P =.001) and 0.45 (95% CI, 0.28-0.72; P =.001) respectively. The correlation was not significant among those with a malnourished status; an HR of 1.06 was calculated for patients with overweight (95% CI, 0.75-1.50; P =.744) and 0.86 for patients with obesity (95% CI, 0.59-1.24; P =.413).

After propensity-score matching, the 90-day risk for death in patients with overweight or obesity was reduced by 50% to 58% among the well-nourished patients. In the malnourished group, overweight or obese status did not demonstrate a significant protective effect, with an HR of 1.09 (95% CI, 0.70-1.71) and an HR of 1.02 (95% CI, 0.66-0.59), respectively. 

Low PNI scores were associated with poorer clinical outcomes in the subgroup analysis. In both the high and low PNI cohorts, patients with overweight or obesity had lower in-hospital and 90-day mortality. Patients with obesity with high PNI scores had the highest cumulative survival rate. 

Because of the retrospective design of the study, a causal relationship could not be determined.

The study authors concluded, “Further exploration and validation of nutritional indicators combined with BMI in a larger population is needed to guide clinicians

on the best strategy for treatment.”

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The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial evaluated the effects of omecamtiv mecarbil in patients with HFrEF. The analysis assessed the efficacy and safety of omecamtiv mecarbil in self-identified Black patients compared with White patients.

Eligible participants were aged 18 to 85 years; had symptomatic HF (New York Heart Association functional class II, III, or IV); had left ventricular EF (LVEF) of 35% or less; had increased natriuretic peptide levels; and were hospitalized for HF, had an urgent visit to the emergency department, or had been hospitalized for HF within 1 year before screening.

The patients were randomly assigned in a 1:1 ratio to receive omecamtiv mecarbil or placebo along with standard care. The omecamtiv mecarbil doses were 25 mg, 37.5 mg, or 50 mg twice daily and were adjusted based on plasma levels of the drug. Postrandomization assessments were conducted at week 2, then every 2 weeks until week 8. After week 8, assessments took place at week 12, 24, 36, 48, and then every 16 weeks.

The primary composite outcome was time to first HF event or death from cardiovascular causes.

A total of 8232 patients were included, of whom 6.8% self-identified as Black. Black patients’ mean age was 58 years, 34% were women, and their mean LVEF was 24%. The mean age among 1129 White patients was 65 years, 24% were women, and their mean LVEF was 25%.

Black patients had 260 primary events (48.6%), and White patients had 484 primary events (42.9%). Black patients were more frequently women, younger, had lower LVEF, were more likely to have hypertension, and were less likely to have atrial arrhythmias or ischemic etiology vs White patients (all P ≤.001).

The primary event rate among Black patients was 38 per 100 patient-years vs 31 per 100 patient-years in White patients (P =.017). The hazard ratio (HR) for primary events in Black vs White patients was 1.33 (95% CI, 1.13-1.56), after adjustment for age, sex, and country. Black patients also had a greater risk for HF hospitalization, with an adjusted HR of 1.38, (95% CI, 1.15-1.65). No significant difference was observed for cardiovascular mortality in the adjusted model (HR, 0.87; 95% CI, 0.67-1.13).

The estimated treatment effect on the primary endpoint for Black patients (HR, 0.83; 95% CI, 0.65-1.06) was comparable to that in White patients in the same countries (HR, 0.88; 95% CI, 0.73-1.05). For absolute event rates, the estimated effect of omecamtiv mecarbil for Black patients was a decreased primary event rate of 7.7 events per 100 patient-years (95% CI, -17.9 to 2.4) vs saving 6.0 events per 100 patient-years in White patients (95% CI, -11.9 to 0.0).

The investigators noted that the only nominally significant interaction between treatment and race that effected clinical outcomes was in blood pressure. In Black patients, omecamtiv mecarbil was associated with a 3.4-mm Hg increase in systolic blood pressure (95% CI, 0.2-6.7). For White patients, no significant change in systolic blood pressure occurred (-0.7 mm Hg; 95% CI, 2.6-1.3), with an unadjusted interaction P-value of .02.

The researchers noted that the trial was not designed to be adequately powered for race-based stratified analyses of the primary and secondary endpoints, and they did not have data on socioeconomic status or other social determinants of health.

“These data underscore the importance of diverse patient enrollment in clinical trials, specifically including groups that are traditionally under-represented such as Black patients, so patients and providers can have confidence that overall study findings can be safely applied to these subgroups,” wrote the investigators.

Disclosure: The GALACTIC-HF trial was funded by Amgen, Cytokinetics Inc, and Servier Laboratories. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Kensuke Ueno, P.T., from the Kitasato University Graduate School of Medical Sciences in Sagamihara, Japan, and colleagues examined the association between QIS, as a measure of skeletal muscle strength, and the risk for developing heart failure among 932 AMI patients without a history of heart failure or complications of heart failure during hospitalization.

The researchers found that 67 patients (7.2 percent) developed heart failure during an average follow-up of 4.5 years. The incidence of heart failure was 10.2 and 22.9 per 1,000 person-years in patients with high and low quadriceps strength, respectively. In adjusted analyses, a high QIS level was associated with a significantly lower risk for developing heart failure compared with low QIS (hazard ratio, 0.59). Each 5 percent body weight increment in QIS was associated with a lower likelihood of heart failure (hazard ratio, 0.89).

“Quadriceps strength is easy and simple to measure accurately in clinical practice. Our study indicates that quadriceps strength could help to identify patients at a higher risk of developing heart failure after myocardial infarction who could then receive more intense surveillance,” Ueno said in a statement. “The findings need to be replicated in other studies, but they do suggest that strength training involving the quadriceps muscles should be recommended for patients who have experienced a heart attack to prevent heart failure.”

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The prospective EPICTER study consecutively enrolled patients admitted for acute HF. Eligible participants were aged older than 18 years, admitted to the hospital before 8:00 am on the day of data collection, and had HF as the main cause of admission. Data came from 74 Spanish hospitals

The primary outcome was all-cause mortality at day 7. Secondary outcomes included all-cause mortality at days 30 and 180, as well as hospital readmissions and emergency room visits, both at 180 days.

The participants were categorized into 2 groups depending on whether they were receiving treatment with BZDs during admission. A descriptive analysis of the data and a propensity score matching analysis were performed.

The analyses included 1855 patients, 639 were prescribed BZDs (34.4%; mean age, 78.7±10.8 years; 51.8% women) compared with 1216 who were not treated with BZDs (65.6%; mean age, 79.8±10.6 years; 52.8% women). Participants in the BZD group had more cardiac comorbidities (myocardial infarction and previous HF) and noncardiac comorbidities (cerebrovascular disease, peripheral artery disease, anemia, and cognitive impairment).

Mortality rates were significantly higher in the group of patients treated with BZDs at 7 days (8.8% vs 3.4%), 30 days (18.3% vs 11.8%), and 180 days (37.1% vs 27.6%). No differences were found for readmissions and visits to the emergency room.

After propensity score calculation, the model showed an area under the receiver operating characteristic curve of 0.71 (95% CI, 0.69-0.74) and a Hosmer-Lemeshow goodness-of-fit test P-value of 0.59. There were 381 balanced paired cases following propensity score matching.

In the propensity-matching cohort, treatment with BZDs was not associated with an increased risk of mortality at day 7 (7.6% vs 5.2%; adjusted odds ratio [aOR], 1.49; 95% CI, 0.83-2.68; P =.186), at 30 days (15.0% vs 15.2%; aOR, 0.98; 95% CI, 0.66-1.96; P =.919), or at 180 days (32.3% vs 30.2%; aOR, 0.91; 95% CI, 0.67-1.23; P =.901).

The patients who received BZDs also did not have an increased rate of readmissions for HF (37.3% vs 37.8%; aOR, 1.02; 95% CI, 0.76-1.37; P =.881) or visits to the emergency room for HF (36.2% vs 31.8%; aOR, 1.22; 95% CI, 090-1.65; P =.194) compared with not taking BZDs.

Limitations of the study include the lack of randomization and unmeasured variables that could have biased the results. Also, differences occurred in the proportion of patients with cerebrovascular disease, and a significant number of patients were enrolled in the EPICTER study with no data on BZD treatment or were lost to follow-up. Furthermore, the study did not assess whether patients had other side effects from the therapy.

“Patients admitted for acute HF taking BZDs have advanced heart disease, severe symptoms, and need more intensive treatment,” wrote the study authors. “In this scenario, our data support that BZDs can be safely used for symptomatic relief.”

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An international team of investigators aimed to explore outcomes among patients with prior HF hospitalization subsequently treated with empagliflozin. The primary composite outcome was time to first HF hospitalization or cardiovascular death.

The researchers conducted a post hoc analysis of the EMPEROR-Pooled trial, which contained data from the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic HFrEF; ClinicalTrials.gov Identifier: NCT03057977) and EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic HFpEF; ClinicalTrials.gov Identifier: NCT03057951) trials.

Combined, these studies included 9718 patients with HF grouped according to how recently they were hospitalized for HF (never [n=6270], <3 months [n=1050], 3-6 months [n=734], 6-12 months [n=736], and >12 months [928]). Patients with a more recent HF hospitalization tended to have lower blood pressure, higher heart rate, higher pro-B-type natriuretic peptide levels, and were more likely to be younger men. Median follow-up time was 21 months.

The primary endpoint event rates per 100 person-years in the placebo group were the following:

• 26.7 in patients in the less than 3 months group
• 18.1 in patients in the 3 to 6 months group
• 13.7 in patients in the 6 to 12 months group
• 2.8 in patients in the over 12 months group

Less than 3% of patients had hospitalization within 1 month of inclusion. A higher risk for primary endpoint events was noted in patients without prior HF hospitalization (10.6) vs patients hospitalized more than 12 months prior to enrollment (2.8).

When patients were treated with empagliflozin, the relative risk reduction for the primary outcome events was similar across all HF hospitalization timing categories (P_interaction =.67).

Among patients with a recent HF hospitalization, the primary endpoint absolute risk reduction (without statistical heterogeneity of treatment effect) in events prevented per 100 person-years were the following:

• -6.9 in patients in the less than 3 months group
• -5.5 in patients in the 3 to 6 months group
• -0.8 in patients in the 6 to 12 months group
• -0.6 in patients in the more than 12 months group
• -2.4 in patients without prior HF hospitalization

Regardless of HF hospitalization timing category, there was an overall neutral effect of empagliflozin on cardiovascular mortality (<3 months [hazard ratio {HR}, 0.71; 95% CI, 0.51-1.00]; 3-6 months [HR, 0.87; 95% CI, 0.55-1.37]; 6-12 months [HR, 1.19; 95% CI, 0.74-1.93]; >12 months [HR, 0.80; 95% CI, 0.43-1.49]).

Limitations of the study include its limited power to assess within-group treatment effects in timing subgroups for prior HF hospitalization, and lack of generalizability to patients hospitalized in the month prior to inclusion.

“Patients with a recent HF hospitalization, particularly if occurring within the previous 3 months, have a high risk of HF rehospitalization and mortality and experience large absolute benefit from empagliflozin treatment,” the study authors wrote. “These findings underscore the importance of initiating empagliflozin as early as possible within or early after an HF hospitalization, if not possible to initiate treatment to prevent a first HF hospitalization.”

Disclosure: This research (The EMPEROR-Reduced and Preserved trials) was supported by Boehringer Ingelheim and Eli Lilly. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Trials of antihyperglycemic therapies have reported various cardiovascular benefits. This review and analysis was designed to assess the effects of newer antihyperglycemic medications on cardiovascular outcomes.

To that end, investigators from Medical Research Institute Kitano Hospital in Japan searched publication databases through January 2023 for randomized trials of antihyperglycemic interventions with MACE outcomes is the setting of type 2 diabetes (T2D) or prediabetes. A total of 35 trials comprising 256,524 patients were included in this analysis.

The interventions included glucagon-like peptide-1 receptor (GLP-1R) agonists (n=9), peroxisome proliferator-activated receptor (PPAR) agonists (n=8), sodium-glucose cotransporter-2 (SGLT2) inhibitors (n=6), dipeptidyl-peptidase-4 (DPP-4) inhibitors (n=5), intensive glycemic control (n=4), intensive lifestyle interventions focusing on weight loss (n=1), insulin glargine (n=1), and acarbose (n=1).

The patients had mean ages of 53.3 to 69.0 years, 66.2% had established atherosclerotic cardiovascular disease, and 13.4% had a history of heart failure (HF).

During follow-up, MACE occurred among 9.9% of patients. Patients that received antihyperglycemic interventions had a 9% reduction in MACE events compared with control patients (risk ratio [RR], 0.91; 95% CI, 0.88-0.94; I², 36.5%; P <.001). Stratified by intervention, MACE was reduced by intensive glycemic control (RR, 0.90; 95% CI, 0.83-0.97; I², 0.0%; P =.008), PPAR agonists (RR, 0.91; 95% CI, 0.84-0.97; I², 25.2%; P =.006), SGLT2 inhibitors (RR, 0.88; 95% CI, 0.82-0.94; I², 28.1%; P <.001), and GLP-1R agonists (RR, 0.87; 95% CI, 0.81-0.94; I², 53.3%; P =.001).

In the metaregression analysis, every 1% greater reduction in HbA_1C was associated with a 14% relative reduction in RR for MACE, explaining 52% of the variance (P =.010), whereas the change in bodyweight from baseline did not have a moderating effect (P =.41).

During follow-up, 3.6% of patients experienced HF outcomes. The antihyperglycemic interventions were not associated with a significant effect on HF overall (RR, 0.95; 95% CI, 0.87-1.04; I², 75.9%; P =.28). Stratified by intervention, significant reductions were associated with SGLT2 inhibitors (RR, 0.68; 95% CI, 0.62-0.75; I², 0.0%; P <.001) and GLP-1R agonists (RR, 0.90; 95% CI, 0.83-0.98; I², 0.0%; P =.019). Conversely, HF risk was increased by 38% with PPAR agonists (RR, 1.38; 95% CI, 1.19-1.60; I², 53.0%; P <.001).

In contrast to the MACE analysis, for every 1 kg greater reduction in bodyweight from baseline, HF risk decreased by 7% (P <.001) and explained 52% of the variance. Whereas HbA_1C changes did not have an effect on HF outcomes (P =.46).

This analysis may be limited by not using individual participant data.

“…glycemic control conferred by a wide range of antihyperglycemic drugs decreases MACE risk in an HbA_1C-dependent manner, and the degree of HbA_1C reduction is a useful surrogate of cardiovascular benefits,” the study authors wrote. “Contrary to MACE risk reduction, HF risk modulation was not associated with HbA_1C reduction but was associated with bodyweight reduction.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

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Researchers presented findings from the myPACE (ClinicalTrials.gov Identifier: NCT04721314) trial, which evaluated moderately accelerated pacing in patients with HFpEF for 1 year.

The prospective, blinded, parallel-group, randomized clinical trial recruited patients with American College of Cardiology/American Heart Association stage B and C HFpEF with an ejection fraction of more than 50%. Participants were enrolled from July 2019 to November 2020, with follow-up concluding in December 2021.

The participants completed baseline assessments and were then randomly assigned in a 1:1 ratio to a personalized backup heart rate setting (myPACE) or the nominal 60-bpm setting (usual care) for 1 year. The primary outcome was the change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score.

A total of 100 patients participated in the study. Of these patients, 52 were in the usual care group and 48 were in the myPACE group. Their median age was 75 (IQR, 69-81) years, 48% were women, and the median H₂FPEF score was 6 (IQR, 5-8). The median baseline pacemaker-recorded heart rate within the previous 6 months was 65 (IQR, 65-70) bpm in the usual care group and 65 (61-70) bpm in the myPACE group. The median programmed rate was 60 (IQR, 60-60) bpm in the usual care group and 75 (IQR, 70-75) bpm in the myPACE group. The resultant median pacemaker-recorded heart rate at 2 years was 65 (IQR, 63-68) bpm in the usual care group and 75 (IQR, 75-80) bpm in the myPACE group.

The mean follow-up was 378 (SD, 83) days. Participants’ mean MLHFQ scores decreased by 0.6 (SD, 9.1) points at 1 month and increased by 3.5 (SD, 10.6) points at 1 year for usual care. MLHFQ scores improved by a mean of 10.9 (SD, 13.7) points at 1 month and 15.0 (SD, 15.5) points at 1 year for the myPACE group. The relative percent change in NT-proBNP levels at 1 month between groups was P =.02.

The median pacemaker-detected daily activity level at baseline was 2.5 (IQR, 2.1-3.9) hours for usual care and 2.6 (IQR, 1.5-3.1) hours for personalized accelerated pacing. At 1 year, daily activity levels were greater with personalized accelerated pacing (median [IQR], 3.1 [2.0-4.3] hours) vs usual care (median [IQR], 2.9 [1.7-4.0] hours; P =.003).

Personalized accelerated pacing reduced the relative risk of device-detected AF by 27% compared with usual care (risk ratio, 0.73; 95% CI, 0.55-0.99; P =.04). With personalized accelerated pacing, 4 participants had 4 adverse events, and with usual care, 11 participants had 17 adverse events.

Study limitations include more than half of the patients had sick sinus syndrome as the primary pacing indication, which may have increased the effect size of the personalized accelerated pacing intervention. Also, although the MLHFQ and NT-proBNP levels are not significantly different, the values are nominally higher in the personalized accelerated pacing group vs usual care. In addition, enrollment stopped early owing to the COVID-19 pandemic.

“The myPACE study supports the concept of heart rate modulation as a therapeutic intervention in HFpEF and provides additional evidence that moderately higher, and not lower, heart rates are beneficial in this complex patient population with an unmet need for therapies addressing underlying hemodynamic and cardiac structural abnormalities,” the investigators wrote.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Investigators sought to compare the incidence of HF in patients with obesity who received bariatric surgery with those that received nonsurgical management. The primary outcome was the development of new HF. Secondary outcomes were hospitalizations due to HF and all-cause mortality.

They conducted a nationwide propensity-score matched retrospective cohort study using patient records from the Clinical Practice Research Database (CPRD), a nationwide UK database of primary care patient records integrated with secondary care data. The CPRD database contains primary care records of more than 19 million patients gathered from 945 general practice surgeries since 1987.

Patients included in the study were aged 18 years or older, had a BMI greater than 35, and no prior diagnosis of HF. Of 146,938 eligible patients, 3111 received bariatric surgery. Of these patients, 59 could not be matched.

Overall, 3052 patients who received bariatric surgery were propensity-score matched with 3052 patients who did not. Patients that received bariatric surgery had a mean age of 44.24 (SD, 10.84), 22.2% were men, and their mean BMI was 42.87 (SD, 6.30).  In the bariatric surgery cohort, 27.6% of patients had hypertension, 23.4% had type 2 diabetes mellitus, and 6.4% had hypercholesterolemia. In the same cohort, 47.8% smoked cigarettes, 1.4% drank alcohol, 24.3% were taking angiotensin-converting enzyme inhibitors, and 19.1% were taking beta-blockers. Duration of mean follow-up was 7.5 years (4.54 years bariatric surgery group; 10.45 years nonbariatric surgery group).

There was a significantly lower incidence of new HF among patients who received bariatric surgery vs those who did not (hazard ratio [HR], 0.45; 95% CI, 0.28-0.73; P =.0011). During follow-up there were 21 HF events in the bariatric surgery cohort and 147 in the nonbariatric surgery cohort.

There was a significantly lower incidence of all-cause mortality among patients who received bariatric surgery vs those who did not (HR, 0.56; 95% CI, 0.38-0.83; P =.0036). There were 33 deaths in the bariatric surgery cohort during follow-up vs 257 deaths in the nonbariatric surgery cohort. In the bariatric surgery cohort, 9.5% of patients that developed HF died compared with 41.5% of patients who developed HF in the nonbariatric surgery cohort.

Study limitations include the possibility of missing data and potential confounding.

 “….our study provides incremental evidence that bariatric surgery is associated with a reduced incidence of heart failure in patients with obesity, in a large nationwide propensity-score matched cohort,” the study authors wrote. “Taken with the wealth of other literature on the potential benefits of bariatric surgery in such patients, we suggest that bariatric surgery represents a crucial weapon in the fight against obesity—and, more widely, the metabolic syndrome.”

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Investigators sought to evaluate quality of care and clinical outcomes among patients hospitalized for HF at rural vs urban hospitals in the US. Primary endpoints included 30-day mortality and readmission outcomes, length of stay, and in-hospital mortality.

They initiated a retrospective observational cohort study from January 2014 through September 2021 that included 19,832 (2.6%) patients hospitalized for HF at rural hospitals and 754,587 (97.4%) patients hospitalized for HF at urban hospitals across 569 sites (49 [8.6%] rural hospitals; 520 [91.4%] urban hospitals) in the Get With the Guidelines-Heart Failure (GWTG-HF) registry. Among these patients, 161,996 had data linked to Medicare claims that were used to evaluate post-discharge outcomes. Patients were at least 18 years of age. Sites missing hospital characteristics data were excluded from the study. Patients discharged to hospice or palliative care, who left on medical advice, or transferred to another acute care facility were excluded, as were patients with missing data for sex, age, or patient disposition.

Rural hospitals were defined as those not located within a metropolitan area designated by the US Office of Management and Budget and the Census Bureau. Investigators reclassified 2.8% of hospitals as either rural or urban based on Rural-Urban Commuting Area code definitions.

Overall, patients were median 73 years of age (IQR, 62-83) and 47.3% women. Patients at rural hospitals vs urban hospitals were more likely to be non-Hispanic White patients (73.5% vs 66.1%; standardized difference, 34.47%) and older (median 74 years [IQR, 64-84] vs median 73 years [IQR, 61-83]; standardized difference, 10.63%). Patients at rural hospitals vs urban hospitals were more likely to have Medicare insurance (58.4% vs 51.1%), higher median ejection fraction (EF) and systolic blood pressure, and lower N-terminal pro-brain natriuretic peptide levels.

At discharge, the investigators found patients at rural hospitals were less likely to be prescribed an angiotensin receptor-neprilysin inhibitor (ARNI; adjusted risk difference [aRD], -5.0%; adjusted odds ratio [aOR], 0.68; 95% CI, 0.47-0.98), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB; aRD, -3.7%; aOR, 0.71; 95% CI, 0.53-0.96), and cardiac resynchronization therapy (CRT; aRD, -13.5%; aOR, 0.44; 95% CI, 0.22-0.92).

Length of stay of 4 days or longer was less likely for patients at rural hospitals (aOR, 0.75; 95% CI, 0.67-0.85). In-hospital mortality between rural vs urban hospitals was similar (2.3% vs 2.7%; aOR, 0.86; 95% CI, 0.70-1.07) and no significant differences were noted between rural vs urban hospitals in 30-day HF readmission among Medicare beneficiaries (adjusted hazard ratio [aHR], 1.03; 95% CI, 0.90-1.19), all-cause mortality (aHR, 1.05; 95% CI, 0.91-1.21), and all-cause readmission (aHR, 0.97; 95% CI, 0.91-1.04). There was no significant interaction between rural hospitals and HF or all-cause readmission. There was a significant interaction between rural status and EF subgroup for all-cause mortality consistent in unadjusted, partially adjusted, and fully adjusted models.

Study limitations include a lack of consensus definition of rural vs urban hospitals. Additionally, potential differences in outpatient HF diagnosis and treatment are not examined, and voluntary participation in GWTG-HF registry may not be representative of rural or urban hospitals.

“In this study of US patients admitted to rural vs urban hospitals for HF, although most quality metrics were similar, patients at rural hospitals were less likely to receive multiple elements of guideline-directed HF care, such as CRT, ACEI/ARB, and ARNI therapies,” the study authors wrote. “Despite these differences in HF care, there were no significant differences between rural and urban hospitals regarding in-hospital mortality or 30-day post-discharge outcomes.”

Disclosure: This research was supported by Novartis, Boehringer Ingelheim and Eli Lilly Diabetes Alliance, Novo Nordisk, Sanofi, AstraZeneca, and Bayer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Researchers reported their findings on the effects of dapagliflozin in Black and White patients across the range of left ventricular ejection fraction (LVEF) in a pooled analysis of 2 clinical trials.

The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) were randomized, double-blind, controlled trials of patients with symptomatic HF and increased natriuretic peptide levels that compared dapagliflozin 10 mg once daily with placebo. Participants with an LVEF of 40% or less were included in the DAPA-HF trial and DELIVER included patients with an LVEF of greater than 40%.

Both trials had the primary outcome of the composite of worsening HF (unplanned HF hospitalization or urgent visit for HF requiring an intravenous diuretic) or cardiovascular death.

Among the 11,007 patients in the trials, 3526 were randomized in North and South America. Of this group, 74.5% identified as White and 10.8% identified as Black or African American. The analysis included only the Black and White patients from the Americas. Compared with White patients, Black patients were much younger (64 vs 70 years), had a higher proportion of women (40.4% vs 34.3%), and were less likely to be current or former smokers.

Worsening HF or cardiovascular death occurred in 19.2% of White patients and 26.5% of Black patients. The event rate per 100 person-years was 11.6 (95% CI, 10.6-12.7) in White patients and 16.8 (95% CI, 13.8-20.4) in Black patients (adjusted hazard ratio [HR], 1.27; 95% CI, 1.01-1.59).

Black patients had a higher rate of worsening HF or cardiovascular death and worsening HF compared with White patients, which was not modified by LVEF (P_interaction ≥.92). The cardiovascular death rate was comparable in Black and White patients and was not modified by LVEF (P_interaction = .67).

Compared with placebo, dapagliflozin decreased the risk for worsening HF or cardiovascular death similarly in Black patients (HR, 0.69; 95% CI, 0.47-1.02) and White patients (HR, 0.73; 95% CI, 0.61-0.88), with no interaction occurring between race and treatment effect (P_interaction =.73).

Dapagliflozin’s number needed to treat to prevent 1 event during the median follow-up was 17 (95% CI, 12-33) for White patients and 12 (95% CI, 9-23) for Black patients.

Regarding safety outcomes, 4.6% of White patients who received dapagliflozin discontinued the drug owing to an adverse event vs 5.4% of Black patients.

Among several limitations, the analyses are not prespecified, and the prespecified inclusion and exclusion criteria in DAPA-HF and DELIVER precluded enrollment of very high-risk patients. In addition, the number and proportion of Black patients are small in both trials, and the association between race and clinical outcomes should be interpreted with caution owing to the observational design and absence of data on social determinants of health.

“…these data underscore the substantial and clinically important benefits, and favorable tolerability and safety profile, of dapagliflozin in patients with HF, across the spectrum of ejection fraction, irrespective of race,” wrote the investigators.

Disclosure: The DAPA-HF and DELIVER trials were funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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Investigators sought to determine whether early administration of dapagliflozin immediately following anterior STEMI would have favorable outcomes for cardiac function.

The prospective, double-blinded, randomized DACAMI (Dapagliflozin on Cardiac Function Following Anterior Myocardial Infarction; ClinicalTrials.gov Identifier: NCT05424315) trial was conducted in Cairo, Egypt. Eligible participants were admitted with anterior STEMI, had echocardiographic evidence of reduced LV ejection fraction (LVEF) of less than 50%, and had successful reperfusion with primary percutaneous coronary angiography (pPCI). Patients with diabetes mellitus types 1 and 2 and those previously diagnosed with heart failure were excluded.

The participants were allocated in a 1:1 ratio into a study group or a control group. The study group received dapagliflozin 10 mg once daily plus guideline-directed medical treatment (GDMT), and the control group received placebo plus GDMT. In the study group, participants received dapagliflozin commencing no later than 72 hours after successful pPCI for STEMI.

The primary outcomes were change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels from baseline to 12 weeks post-anterior STEMI and/or change in LVEF, end-diastolic volume, and/or LV mass index (LVMI) assessed with transthoracic echocardiography at baseline and 4 and 12 weeks post-anterior STEMI.

A total of 100 patients were included from October 2021 to April 2022, 50 patients in the study group and 50 in the control group. The study group had a mean age of 55.24±13.2 years (84% men), and the placebo group had a mean age of 56.70±11.5 years (82% men).

No patients in the study group had a genitourinary infection or hypoglycemic episode. During the 12-week follow-up, 2 patients in either group were hospitalized for heart failure and no mortality occurred.

Baseline median NT-proBNP levels were 290.8 ng/L (IQR, 104.7-387.2) in the study group and 289.4 ng/L (IQR, 92.5-378.6) in the control group (P =.891).

At 12 weeks, the mean reduction in NT-proBNP level was significantly lower for the study group vs the control group by 10.17% (95% CI, -3.28 to 19.67, P =.034).

The study group had a significantly greater change in LVMI vs the control group at 4 and 12 weeks. As early as 4 weeks, LVMI in the study group was less than that in the control group by 7.07% (95% CI, -9.84 to -4.3; P =.032). At 12 weeks, LVMI in the study group was less than that in the control group by 11.46% (95% CI, -19.37 to -3.56; P = .029).

Limitations of the study include the small sample size and that patients were only enrolled from 2 centers. Also, the study depended on objective biomarkers and echocardiographic parameters to derive results, and it is unknown whether this translates into less morbidity and mortality in the future.

“…early administration of dapagliflozin proved to have favorable outcomes on cardiac function, as evidenced by a significant drop in NT-proBNP levels and a significant decrease in LV mass index in the study group compared to the control group,” the investigators wrote.

Disclosure: The NT-proBNP ELISA kits were provided by Inspire Pharma. Please see the original reference for a full list of disclosures.

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Although opioids are recommended to treat breathlessness in patients with advanced heart failure, meta-analyses to support these recommendations have been lacking. Investigators from Germany and Switzerland therefore conducted a systematic review and meta-analysis to assess the effects of opioids on breathlessness in patients with advanced HF.

The investigators searched publication databases through July 2021 for randomized controlled trials evaluating the use of opioids in HF. A total of 8 trials published between 1997 and 2020 were included in this analysis. Most trials had cross-over designs (n=7). The pooled sample size was 271 patients.

The researchers found no significant difference in treatment effect (standardized mean difference [SMD], 0.03; 95% CI, -0.21 to 0.28; I², 0%) when breathlessness was treated with opioids (n=151 patients) vs placebo (n=120 patients).

Quality of life, a secondary outcome of interest in the meta-analysis, was reported on by 4 studies. Here, too, investigators found no significant differences in patients treated with opioids vs control group patients.

With respect to adverse events, opioids were not associated with increased risk for nausea (risk ratio [RR], 3.13; 95% CI, 0.70-14.07; I², 7%) or respiratory rate changes (mean difference [MD], 0.25; 95% CI, -1.22 to 0.72 breaths/minute). However, opioid use vs placebo was more strongly associated with constipation (RR, 4.77; 95% CI, 1.98-11.53; I², 0%), vomiting (RR, 4.29; 95% CI, 1.15-16.01; I², 0%), changes to heart rate (MD, -4.90; 95% CI, -8.90 to -0.90 bpm), and changes in arterial oxygen saturation (MD, -0.92%; 95% CI, -1.79% to -0.06%).

The major limitation of this analysis was the small number of studies and the small sample size.

Overall, said study authors, these data did not support the use of opioids in the setting of HF. “This systematic review questions the benefits of opioids for the treatment of breathlessness in patients with HF. We suggest that opioids may only be the very last option if all options have failed or in case of an emergency,” the investigators concluded.

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Researchers sought to evaluate the association between change in NT-proBNP levels and risk for incident HF and death. The primary outcomes were incident HF and all-cause death. NT-proBNP level change between study visits 2 and 4 was the primary exposure variable.

The researchers conducted the Atherosclerosis Risk in Community (ARIC) study, an observational prospective cohort study that included 9776 individuals (age 45-64 years) recruited from 4 communities in the United States from 1987 to 1989. Participants with measurements of NT-proBNP without prevalent HF who attended ARIC visits 2 (1990-1992) and 4 (approximately 6 years after visit 2) were included in the study.

Individuals with prevalent HF at visit 4, missing NT-proBNP measurements at either visit, race other than Black or White, and Black race from Minnesota and Washington county centers were excluded. Assays were conducted at the University of Minnesota between 2011 and 2013 using stored serum from visit 2 and at Baylor College of Medicine in 2010 using stored plasma from visit 4. Analysis occurred between July 2021 and October 2022.

Median NT-proBNP level at visit 2 was 49.4 pg/mL (IQR, 26.2-88.4) and at visit 4 it was 75.3 pg/mL (IQR, 41.5-136.2). At visit 2, patients were stratified into 2 groups, those with NT-proBNP levels of less than 125 pg/mL (n=8437) and those with NT-proBNP levels of 125 pg/mL or higher (n=1339). The median change in NT-proBNP levels during the period between visits was 21.8 pg/mL (IQR, 0.5-59.3). At visit 2, among participants with NT-proBNP levels of less than 125 pg/mL, the median change in NT-proBNP level was 22.2 pg/mL (IQR, 3.2-55.1). Among participants with NT-proBNP levels of 125 pg/mL or higher, the median change in NT-proBNP level was 12.7 pg/mL (IQR, -57.6 to 121.3).

Overall, participants had hypertension (45.6%), diabetes (15.4%), and prevalent coronary heart disease (7.1%) at visit 4. Over a median follow-up of 20 years, there were 2088 incident HF events and 4493 deaths.

Among all participants (mean age at visit 2, 57.1±5.7 years; 56.5% women; 21.3% Black), those with NT-proBNP levels of 125 pg/mL or higher at both visits had an increase in incident HF (adjusted hazard ratio [aHR], 2.40; 95% CI, 2.00-2.88) and mortality risk (aHR, 1.68; 95% CI, 1.47-1.91) compared with participants with NT-proBNP level of less than 125 pg/mL at both visits.

Compared with participants with a NT-proBNP level of less than 125 pg/mL at both visits, participants with NT-proBNP levels of 125 pg/mL or higher at visit 2 and less than 125 pg/mL at visit 4 had similar risk for HF (aHR, 1.01; 95% CI, 0.71-1.43) and death (HR, 0.79; 95% CI, 0.61-1.01).

Per 1 standard deviation increase, the percent change in NT-proBNP level was positively associated with HF (aHR, 1.06; 95% CI, 1.02-1.10) and death (aHR, 1.05; 95% CI, 1.03-1.08). Researchers noted that changes in estimated glomerular filtration rate, body mass index, triglyceride level, low-density lipoprotein cholesterol, and systolic blood pressure were significantly associated with NT-proBNP change.

Study limitations include the observational study design and potential fluctuations in biomarkers between the 2 time points.

“…NT-proBNP change was associated with risk for incident HF events and all-cause mortality among middle-aged adults without clinical HF independent of cardiovascular risk factors,” the researchers wrote. “Our results support the utility of serial NT-proBNP measurements to predict cardiovascular risk in asymptomatic community-dwelling individuals, especially among patients with pre-HF, and may help guide therapeutic interventions to reduce the likelihood of progression to clinical HF.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

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